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Kong G, Noe G, Chiang C, Herrmann K, Hope TA, Michael M. Assessment of response to PRRT including anatomical and molecular imaging as well as novel biomarkers. J Neuroendocrinol 2025; 37:e13461. [PMID: 39520276 PMCID: PMC11919480 DOI: 10.1111/jne.13461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 09/05/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
Peptide receptor radionuclide therapy (PRRT) is an effective treatment for both oncological and hormone control and is a widely accepted standard of care treatment for patients with neuroendocrine neoplasms (NEN). Its use is anticipated to increase significantly, and this demands accurate tools and paradigms to assess treatment response post PRRT. This article outlines the current role and future developments of anatomical, molecular imaging and biomarkers for response assessment to PRRT, highlighting the challenges and provides perspectives for the need to focus on a multimodality, multidisciplinary and individualised approach for patients with this complex heterogeneous disease.
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Affiliation(s)
- Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear MedicinePeter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneVictoriaAustralia
| | - Geertje Noe
- Department of Cancer ImagingPeter MacCallum Cancer CentreMelbourneVictoriaAustralia
| | - Cherie Chiang
- Department of Internal MedicinePeter MacCallum Cancer CentreParkvilleVictoriaAustralia
- Department of Diabetes and Endocrinology, Melbourne HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Ken Herrmann
- Department of Nuclear MedicineUniversity of Duisburg‐Essen and German Cancer Consortium (DKTK)‐University Hospital EssenEssenGermany
| | - Thomas A. Hope
- Department of RadiologySan Francisco VA Medical CenterSan FranciscoCaliforniaUSA
- Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Michael Michael
- Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneVictoriaAustralia
- Department of Medical OncologyPeter MacCallum Cancer CentreMelbourneVictoriaAustralia
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2
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Massironi S, Albertelli M, Hasballa I, Paravani P, Ferone D, Faggiano A, Danese S. "Cold" Somatostatin Analogs in Neuroendocrine Neoplasms: Decoding Mechanisms, Overcoming Resistance, and Shaping the Future of Therapy. Cells 2025; 14:245. [PMID: 39996718 PMCID: PMC11854070 DOI: 10.3390/cells14040245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 01/28/2025] [Accepted: 02/04/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) represent a heterogeneous group of tumors that pose significant therapeutic challenges due to their potential for progression, metastasis, and hormonal syndromes. Somatostatin analogs (SSAs) have emerged as a cornerstone in NEN treatment, offering both antisecretory and antiproliferative effects by targeting somatostatin receptors (SSTRs). Despite their proven efficacy, intrinsic and acquired resistance mechanisms, including receptor downregulation, tumor heterogeneity, and microenvironmental influences, limit their long-term effectiveness. Recent advances, including high-dose SSA regimens and novel formulations, have aimed to optimize their therapeutic utility and address these limitations. Body of the review. This review explores the cellular and molecular mechanisms underlying the antitumor effects of SSAs, including receptor-mediated signaling pathways, cell cycle arrest, apoptosis induction, and antiangiogenesis. The role of SSAs in combination therapies with mTOR inhibitors and peptide receptor radionuclide therapy (PRRT) is analyzed, emphasizing their synergistic potential. Key clinical trials, such as RADIANT-2, EVERLAR, and NETTER-1, support the efficacy of these approaches, demonstrating improved outcomes when SSAs are combined with targeted agents or radiolabeled therapies. Emerging strategies include high-dose SSA regimens, particularly in progressive cases with low Ki67 indices. Finally, novel formulations, including oral octreotide, paltusotine, and subcutaneous depot formulations like CAM2029, offer improved pharmacokinetics, bioavailability, and patient adherence. Ongoing clinical trials, including SORENTO, further evaluate their efficacy and safety profiles. CONCLUSIONS This paper provides a comprehensive analysis of the cellular and molecular mechanisms of SSAs. SSAs remain integral to the management of NENs, providing effective tumor stabilization and symptom control. However, resistance mechanisms and tumor heterogeneity necessitate innovative approaches, including high-dose regimens, combination strategies, and next-generation formulations. Future research should focus on refining these strategies to optimize patient outcomes, enhance long-term efficacy, and expand the therapeutic landscape for NENs.
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Affiliation(s)
- Sara Massironi
- Faculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy;
- Gastroenterology Unit, Istituti Ospedalieri Bergamaschi, 24046 Bergamo, Italy
| | - Manuela Albertelli
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
| | - Iderina Hasballa
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
| | - Piero Paravani
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant’Andrea Hospital, Sapienza University, 00189 Rome, Italy; (P.P.); (A.F.)
| | - Diego Ferone
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy (I.H.); (D.F.)
| | - Antongiulio Faggiano
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant’Andrea Hospital, Sapienza University, 00189 Rome, Italy; (P.P.); (A.F.)
| | - Silvio Danese
- Faculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy;
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy
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Isik EG, Has Simsek D, Gul N, Erturk SM, Buyukkaya F, Soyluk Selcukbiricik O, Iscan AY, Özkan ZG, Sanli Y, Mudun A, Kuyumcu S. Head-to-Head Comparison of 68Ga-FAPI-04 and 68Ga-DOTA-TATE PET/CT in Recurrent Medullary Thyroid Cancer. Clin Nucl Med 2025; 50:e80-e86. [PMID: 39774161 DOI: 10.1097/rlu.0000000000005558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
PURPOSE We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC). PATIENTS AND METHODS Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated. RESULTS The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas. CONCLUSIONS FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases.
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Affiliation(s)
| | | | | | | | | | | | - Ahmet Yalin Iscan
- Division of Endocrine Surgery, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Nazar AK, Basu S. Radiolabeled Somatostatin Analogs for Cancer Imaging. Semin Nucl Med 2024; 54:914-940. [PMID: 39122608 DOI: 10.1053/j.semnuclmed.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 07/01/2024] [Indexed: 08/12/2024]
Abstract
Somatostatin receptors (SSTR) are expressed by many tumours especially those related to neuro-endocrine origin and molecular functional imaging of SSTR expression using radiolabelled somatostatin analogs have revolutionized imaging of patients with these group of malignancies. Coming a long way from the first radiolabelled somatostatin analog 123I-Tyr-3-octreotide, there has been significant developments in terms of radionuclides used, the ligands and somatostatin derivatives. 111In-Pentetreotide extensively employed for imaging NETs at the beginning has now been replaced by 68Ga-SSA based PET-CT. SSA-PET/CT performs superior to conventional imaging modalities and has evolved in the mainframe for NET imaging. The advantages were multiple: (i) superior spatial resolution of PET versus SPECT, (ii) quantitative capabilities of PET aiding in disease activity and treatment response monitoring with better precision, (iii) shorter scan time and (iv) less patient exposure to radiation. The modality is indicated for staging, detecting the primary in CUP-NETs, restaging, treatment planning (along with FDG: the concept of dual-tracer PET-CT) as well as treatment response evaluation and follow-up of NETs. SSA PET/CT has also been incorporated in the guidelines for imaging of Pheochromocytoma-Paraganglioma, Medullary carcinoma thyroid, Meningioma and Tumor induced osteomalacia. At present, there is rising interest on (a) 18F-labelled SSA, (b) 64Cu-labelled SSA, and (c) somatostatin antagonists. 18F offers excellent imaging properties, 64Cu makes delayed imaging feasible which has implications in dosimetry and SSTR antagonists bind with the SST receptors with high affinity and specificity, providing high contrast images with less background, which can be translated to theranostics effectively. SSTR have been demonstrated in non-neuroendocrine tumours as well in the peer-reviewed literature, with studies demonstrating the potential of SSA PET/CT in Neuroblastoma, Nasopharyngeal carcinoma, carcinoma prostate (neuroendocrine differentiation) and lymphoma. This review will focus on the currently available SSAs and their history, different SPECT/PET agents, SSTR antagonists, comparison between the various imaging tracers, and their utility in both neuroendocrine and non-neuroendocrine tumors.
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Affiliation(s)
- Aamir K Nazar
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai; Homi Bhabha National Institute, Mumbai
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai; Homi Bhabha National Institute, Mumbai.
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Berger F, Ingenerf M, Auernhammer CJ, Cyran C, Ebner R, Zacherl M, Ricke J, Schmid-Tannwald C. [Imaging of pancreatic neuroendocrine tumors]. RADIOLOGIE (HEIDELBERG, GERMANY) 2024; 64:559-567. [PMID: 38789854 DOI: 10.1007/s00117-024-01316-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/24/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Neuroendocrine tumors of the pancreas have a broad biological spectrum. The treatment decision is based on an optimal diagnosis with regard to the local findings and possible locoregional and distant metastases. In addition to purely morphologic imaging procedures, functional parameters are playing an increasingly important role in imaging. OBJECTIVES Prerequisites for optimal imaging of the pancreas, technical principles are provided, and the advantages and disadvantages of common cross-sectional imaging techniques as well as clinical indications for these special imaging methods are discussed. MATERIALS AND METHODS Guidelines, basic and review papers will be analyzed. RESULTS Neuroendocrine tumors of the pancreas have a broad imaging spectrum. Therefore, there is a need for multimodality imaging in which morphologic and functional techniques support each other. While positron emission tomography/computed tomography (PET/CT) can determine the presence of one or more lesions and its/their functional status of the tumor, magnetic resonance imaging (MRI) efficiently identifies the location, relationship to the main duct and the presence of liver metastases. CT allows a better vascular evaluation, even in the presence of anatomical variants as well as sensitive detection of lung metastases. CONCLUSIONS Knowledge of the optimal combination of imaging modalities including clinical and histopathologic results and dedicated imaging techniques is essential to achieve an accurate diagnosis to optimize treatment decision-making and to assess therapy response.
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Affiliation(s)
- Frank Berger
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland
| | - Maria Ingenerf
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland
| | - Christoph J Auernhammer
- Medizinische Klinik und Poliklinik 4, Klinikum der Universität München, LMU München, München, Deutschland
- Interdiziplinäres Zentrum für Neuroendokrine Tumoren des GastroEnteroPankreatischen Systems GEPNET-KUM (ENETS certified CoE), München, Deutschland
| | - Clemens Cyran
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland
- Interdiziplinäres Zentrum für Neuroendokrine Tumoren des GastroEnteroPankreatischen Systems GEPNET-KUM (ENETS certified CoE), München, Deutschland
| | - Ricarda Ebner
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland
| | - Mathias Zacherl
- Klinik für Nuklearmedizin, Klinikum der Universität München, LMU München, München, Deutschland
- Interdiziplinäres Zentrum für Neuroendokrine Tumoren des GastroEnteroPankreatischen Systems GEPNET-KUM (ENETS certified CoE), München, Deutschland
| | - Jens Ricke
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland
- Interdiziplinäres Zentrum für Neuroendokrine Tumoren des GastroEnteroPankreatischen Systems GEPNET-KUM (ENETS certified CoE), München, Deutschland
| | - Christine Schmid-Tannwald
- Klinik und Poliklinik für Radiologie, Klinikum der Universität München, LMU München, München, Deutschland.
- Interdiziplinäres Zentrum für Neuroendokrine Tumoren des GastroEnteroPankreatischen Systems GEPNET-KUM (ENETS certified CoE), München, Deutschland.
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Hesami M, Blake M, Anderson MA, Asmundo L, Kilcoyne A, Najmi Z, Caravan PD, Catana C, Czawlytko C, Esfahani SA, Kambadakone AR, Samir A, McDermott S, Domachevsky L, Ursprung S, Catalano OA. Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses. J Comput Assist Tomogr 2024; 48:521-532. [PMID: 38657156 PMCID: PMC11245376 DOI: 10.1097/rct.0000000000001615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.
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Affiliation(s)
- Mina Hesami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Michael Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Mark A. Anderson
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Luigi Asmundo
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Milan, Italy
| | - Aoife Kilcoyne
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Zahra Najmi
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Peter D. Caravan
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ciprian Catana
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Cynthia Czawlytko
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shadi Abdar Esfahani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Avinash R. Kambadakone
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Anthony Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shaunagh McDermott
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Liran Domachevsky
- Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Onofrio A. Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Asmundo L, Rizzetto F, Blake M, Anderson M, Mojtahed A, Bradley W, Shenoy-Bhangle A, Fernandez-del Castillo C, Qadan M, Ferrone C, Clark J, Ambrosini V, Picchio M, Mapelli P, Evangelista L, Leithner D, Nikolaou K, Ursprung S, Fanti S, Vanzulli A, Catalano OA. Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers. J Clin Med 2024; 13:3281. [PMID: 38892992 PMCID: PMC11172657 DOI: 10.3390/jcm13113281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/23/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.
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Affiliation(s)
- Luigi Asmundo
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy;
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Francesco Rizzetto
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy;
- Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy;
| | - Michael Blake
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Mark Anderson
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Amirkasra Mojtahed
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - William Bradley
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Anuradha Shenoy-Bhangle
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Carlos Fernandez-del Castillo
- Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (C.F.-d.C.); (M.Q.)
| | - Motaz Qadan
- Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (C.F.-d.C.); (M.Q.)
| | - Cristina Ferrone
- Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA;
| | - Jeffrey Clark
- Department of Oncology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;
| | - Valentina Ambrosini
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (V.A.); (S.F.)
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Maria Picchio
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy; (M.P.); (P.M.)
| | - Paola Mapelli
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy; (M.P.); (P.M.)
| | - Laura Evangelista
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
| | - Doris Leithner
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany;
| | - Konstantin Nikolaou
- Department of Radiology, University Hospital Tuebingen, Osianderstraße 5, 72076 Tübingen, Germany; (K.N.); (S.U.)
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Osianderstraße 5, 72076 Tübingen, Germany; (K.N.); (S.U.)
| | - Stefano Fanti
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (V.A.); (S.F.)
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Angelo Vanzulli
- Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy;
- Department of Oncology and Hemato-Oncology, Università Degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Onofrio Antonio Catalano
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
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Fainstein-Day P, Ullmann TE, Dalurzo MCL, Sevlever GE, Smith DE. The clinical and biochemical spectrum of ectopic acromegaly. Best Pract Res Clin Endocrinol Metab 2024; 38:101877. [PMID: 38413286 DOI: 10.1016/j.beem.2024.101877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Ectopic acromegaly is a rare condition caused by extrapituitary central or peripheral neuroendocrine tumours (NET) that hypersecrete GH or, more commonly, GHRH. It affects less than 1% of acromegaly patients and a misdiagnosis of classic acromegaly can lead to an inappropriate pituitary surgery. Four types of ectopic acromegaly have been described: 1) Central ectopic GH-secretion: Careful cross-sectional imaging is required to exclude ectopic pituitary adenomas. 2) Peripheral GH secretion: Extremely rare. 3) Central ectopic GHRH secretion: Sellar gangliocytomas immunohistochemically positive for GHRH are found after pituitary surgery. 4) Peripheral GHRH secretion: The most common type of ectopic acromegaly is due to peripheral GHRH-secreting NETs. Tumours are large and usually located in the lungs or pancreas. Pituitary hyperplasia resulting from chronic GHRH stimulation is difficult to detect or can be misinterpreted as pituitary adenoma in the MRI. Measurement of serum GHRH levels is a specific and useful diagnostic tool. Surgery of GHRH-secreting NETs is often curative.
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Affiliation(s)
- Patricia Fainstein-Day
- Endocrinology, Metabolism and Nuclear Medicine Department, Hospital Italiano de Buenos Aires (HIBA), Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Universitario del Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, Buenos Aires, CP C1199ABB, Argentina.
| | - Tamara Estefanía Ullmann
- Endocrinology, Metabolism and Nuclear Medicine Department, Hospital Italiano de Buenos Aires (HIBA), Tte. Gral. Juan Domingo Perón 4190, Buenos Aires, CP C1199ABB, Argentina.
| | - Mercedes Corina Liliana Dalurzo
- Pathology Department, Hospital Italiano de Buenos Aires (HIBA), Tte. Gral. Juan Domingo Perón 4190, Buenos Aires, CP C1199ABB, Argentina.
| | - Gustavo Emilio Sevlever
- Department of Neuropathology and Molecular Biology. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Montañeses 2325, C1428AQK Buenos Aires, Argentina.
| | - David Eduardo Smith
- General Surgery Department, Hospital Italiano de Buenos Aires (HIBA), Argentina.
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Lin H, Li Y, Chen Y, Zeng L, Li B, Chen S. Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor: A SEER-Based Study. Pancreas 2024; 53:e424-e433. [PMID: 38530947 DOI: 10.1097/mpa.0000000000002320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
OBJECTIVES Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood. MATERIALS AND METHODS The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients. RESULTS The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C -indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively. CONCLUSIONS The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.
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Affiliation(s)
- Hai Lin
- From the Department of Cancer Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province, China
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10
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Liu Y, Cui R, Wang Z, Lin Q, Tang W, Zhang B, Li G, Wang Z. Evaluating Prognosis of Gastrointestinal Metastatic Neuroendocrine Tumors: Constructing a Novel Prognostic Nomogram Based on NETPET Score and Metabolic Parameters from PET/CT Imaging. Pharmaceuticals (Basel) 2024; 17:373. [PMID: 38543159 PMCID: PMC10975134 DOI: 10.3390/ph17030373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/27/2024] [Accepted: 03/07/2024] [Indexed: 01/06/2025] Open
Abstract
INTRODUCTION The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. METHODS In this retrospective study, G1-G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. RESULTS In this study, 223 patients (130 males; mean age ± SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1-D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). CONCLUSIONS New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts.
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Affiliation(s)
- Yifan Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Ruizhe Cui
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Qi Lin
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Wei Tang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Bing Zhang
- Department of Nuclear Medicine, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China;
| | - Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
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11
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Bonazzi N, Fortunati E, Zanoni L, Argalia G, Calabrò D, Tabacchi E, Allegri V, Campana D, Andrini E, Lamberti G, Di Franco M, Casadei R, Ricci C, Mosconi C, Fanti S, Ambrosini V. Real-Life Use of [68Ga]Ga-DOTANOC PET/CT in Confirmed and Suspected NETs from a Prospective 5-Year Electronic Archive at an ENETS Center of Excellence: More Than 2000 Scans in More Than 1500 Patients. Cancers (Basel) 2024; 16:701. [PMID: 38398092 PMCID: PMC10886517 DOI: 10.3390/cancers16040701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.
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Affiliation(s)
- Norma Bonazzi
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
| | - Emilia Fortunati
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
| | - Lucia Zanoni
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
| | - Giulia Argalia
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
| | - Diletta Calabrò
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
| | - Elena Tabacchi
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
| | - Vincenzo Allegri
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
| | - Davide Campana
- Medical Oncology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.C.); (E.A.); (G.L.)
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
| | - Elisa Andrini
- Medical Oncology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.C.); (E.A.); (G.L.)
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
| | - Giuseppe Lamberti
- Medical Oncology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.C.); (E.A.); (G.L.)
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
| | - Martina Di Franco
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
| | - Riccardo Casadei
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (R.C.); (C.R.)
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (R.C.); (C.R.)
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Cristina Mosconi
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy;
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Stefano Fanti
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy; (G.A.); (D.C.); (M.D.F.); (S.F.); (V.A.)
- Nuclear Medicine, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (E.F.); (L.Z.); (E.T.); (V.A.)
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12
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Alobuia WM, Kebebew E. Anatomical and Functional Imaging in the Management of VHL-Associated Pancreatic Lesions. VON HIPPEL-LINDAU DISEASE 2024:173-185. [DOI: 10.1007/978-3-031-53858-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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13
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Nuttall R, Pham TT, Chadwick AC, Hungnes IN, Firth G, Heckenast MA, Sparkes HA, Galan MC, Ma MT, Pringle PG. Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules. Inorg Chem 2023; 62:20582-20592. [PMID: 36719138 PMCID: PMC10731653 DOI: 10.1021/acs.inorgchem.2c04008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Indexed: 02/01/2023]
Abstract
The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph2PCH2CH2P(CH2CH2-Glc)2 (L, where Glc = a glucose moiety) using the readily accessible Ph2PCH2CH2PH2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis- and trans-[M(O)2L2]+ (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[99mTc(O)2L2]+ and trans-[99mTc(O)2L2]+ exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.
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Affiliation(s)
- Rachel
E. Nuttall
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
- School
of Biomedical Engineering and Imaging Sciences, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom
| | - Truc Thuy Pham
- School
of Biomedical Engineering and Imaging Sciences, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom
| | - Ailis C. Chadwick
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
| | - Ingebjørg N. Hungnes
- School
of Biomedical Engineering and Imaging Sciences, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom
| | - George Firth
- School
of Biomedical Engineering and Imaging Sciences, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom
| | - Martin A. Heckenast
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
| | - Hazel A. Sparkes
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
| | - M. Carmen Galan
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
| | - Michelle T. Ma
- School
of Biomedical Engineering and Imaging Sciences, King’s College London, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, United Kingdom
| | - Paul G. Pringle
- School
of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom
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14
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Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
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Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
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15
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Said M, Krogh J, Feldt-Rasmussen U, Rasmussen ÅK, Kristensen TS, Rossing CM, Johannesen HH, Oturai P, Holmager P, Kjaer A, Klose M, Langer S, Knigge U, Andreassen M. Imaging surveillance in multiple endocrine neoplasia type 1: Ten years of experience with somatostatin receptor positron emission tomography. J Neuroendocrinol 2023; 35:e13322. [PMID: 37564005 DOI: 10.1111/jne.13322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 06/23/2023] [Accepted: 06/29/2023] [Indexed: 08/12/2023]
Abstract
Guidelines for multiple endocrine neoplasia type 1 (MEN1) recommend intensive imaging surveillance without specifying a superior regimen, including the role of somatostatin receptor imaging (SRI) with positron emission tomography (PET). The primary outcomes were to: (1) Assess change in treatment of duodenal-pancreatic neuroendocrine neoplasms (DP-NENs), bronchopulmonary NENs, and thymic tumors attributed to use of SRI PET/computed tomography (CT) and (2) estimate radiation from imaging and risk of cancer death attributed to imaging radiation. This was a retrospective single center study, including all MEN1 patients, who had had at least one SRI PET/CT. A total of 60 patients, median age 42 (range 21-54) years, median follow-up 6 (range 1-10) years were included. Of 470 cross sectional scans (MRI, CT, SRI PET/CT), 209 were SRI PET/CT. The additional information from SRI PET had implications in 1/14 surgical interventions and 2/12 medical interventions. The estimated median radiation dose per patient was 104 (range 51-468) mSv of which PET contributed with 13 (range 5-55) mSv and CT with 91 mSv (range 46-413 mSv), corresponding to an estimated increased median risk of cancer death of 0.5% during 6 years follow-up. SRI PET had a significant impact on 3/26 decisions to intervene in 60 MEN1 patients followed for a median of 6 years with SRI PET/CT as the most frequently used modality. The surveillance program showed a high radiation dose. Multi-modality imaging strategies designed to minimize radiation exposure should be considered. Based on our findings, SRI-PET combined with CT cannot be recommended for routine surveillance in MEN1 patients.
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Affiliation(s)
- Maha Said
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Jesper Krogh
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Ulla Feldt-Rasmussen
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Åse Krogh Rasmussen
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | | | - Caroline Maria Rossing
- Department of Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Helle Hjorth Johannesen
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Peter Oturai
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Pernille Holmager
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Marianne Klose
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Seppo Langer
- Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Ulrich Knigge
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
- Department of surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
| | - Mikkel Andreassen
- Department of Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen N, Denmark
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16
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Adnan A, Basu S. Somatostatin Receptor Targeted PET-CT and Its Role in the Management and Theranostics of Gastroenteropancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2023; 13:2154. [PMID: 37443548 DOI: 10.3390/diagnostics13132154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/18/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Somatostatin receptor (SSTR) agonist-based Positron Emission Tomography-Computed Tomography (PET-CT) imaging is nowadays the mainstay for the assessment and diagnostic imaging of neuroendocrine neoplasms (NEN), especially in well-differentiated neuroendocrine tumors (NET) (World Health Organization (WHO) grade I and II). Major clinical indications for SSTR imaging are primary staging and metastatic workup, especially (a) before surgery, (b) detection of unknown primary in metastatic NET, (c) patient selection for theranostics and appropriate therapy, especially peptide receptor radionuclide therapy (PRRT), while less major indications include treatment response evaluation on and disease prognostication. Dual tracer PET-CT imaging using SSTR targeted PET tracers, viz. [68Ga]Ga-DOTA-Tyr3-Octreotate (DOTA-TATE) and [68Ga]Ga-DOTA-NaI3-Octreotide (DOTA-NOC), and fluorodeoxyglucose (FDG), have recently gained widespread acceptance for better assessment of whole-body tumor biology compared to single-site histopathology, in terms of being non-invasive and the ability to assess inter- and intra-tumoral heterogeneity on a global scale. FDG uptake has been identified as independent adverse risk factor in various studies. Recently, somatostatin receptor antagonists have been shown to be more sensitive and specific in detecting the disease. The aim of this review article is to summarize the clinical importance of SSTR-based imaging in the clinical management of neuroendocrine and related tumors.
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Affiliation(s)
- Aadil Adnan
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, JerbaiWadia Road, Parel, Mumbai 400012, India
- Homi Bhabha National Institute, Mumbai 400094, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, JerbaiWadia Road, Parel, Mumbai 400012, India
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17
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Haidar M, Al Mahmasani L, Chehade L, Elias C, El Jebai M, Temraz S, Charafeddine M, Al Darazi M, Shamseddine A. Well-differentiated gastro-entero-pancreatic neuroendocrine tumors with positive FDG-PET/CT: a retrospective chart review. Nucl Med Commun 2023; 44:471-479. [PMID: 36897058 DOI: 10.1097/mnm.0000000000001683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
PURPOSE Rarely, well-differentiated gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) can have positive uptake on 18F-fluorodeoxyglucose-PET/computerized tomography ( 18 F-FDG-PET/CT), with or without a positive 68 Ga-PET/CT. We aim to evaluate the diagnostic role of 18 F-FDG-PET/CT in patients with well-differentiated GEP NETs. METHODS We retrospectively reviewed a chart of patients diagnosed with GEP NETs between 2014 and 2021, at the American University of Beirut Medical Center, who have low (G1; Ki-67 ≤2) or intermediate (G2; and Ki-67 >2-≤20) well-differentiated tumors with positive findings on FDG-PET/CT. The primary endpoint is progression-free survival (PFS) compared to historical control, and the secondary outcome is to describe their clinical outcome. RESULTS In total 8 out of 36 patients with G1 or G2 GEP NET met the inclusion criteria for this study. The median age was 60 years (range 51-75 years) and 75% were male. One patient (12.5%) had a G1 tumor whereas 7 (87.5%) had G2, and seven patients were stage IV. The primary tumor was intestinal in 62.5% of the patients and pancreatic in 37.5%. Seven patients had both 18 F-FDG-PET/CT and 68 Ga-PET/CT positive and one patient had a positive 18 F-FDG-PET/CT and negative 68 Ga-PET/CT. Median and mean PFS in patients positive for both 68 Ga-PET/CT and 18 F-FDG-PET/CT were 49.71 months and 37.5 months (95% CI, 20.7-54.3), respectively. PFS in these patients is lower than that reported in the literature for G1/G2 NETs with positive 68 Ga-PET/CT and negative FDG-PET/CT (37.5 vs. 71 months; P = 0.0217). CONCLUSION A new prognostic score that includes 18 F-FDG-PET/CT in G1/G2 GEP NETs could identify more aggressive tumors.
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Affiliation(s)
| | - Layal Al Mahmasani
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Laudy Chehade
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Charbel Elias
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | | | - Sally Temraz
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maya Charafeddine
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Monita Al Darazi
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
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Sulciner ML, Clancy TE. Surgical Management of Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2023; 15:2006. [PMID: 37046665 PMCID: PMC10093271 DOI: 10.3390/cancers15072006] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.
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Affiliation(s)
| | - Thomas E. Clancy
- Division of Surgical Oncology, Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
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19
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Relevance of Volumetric Parameters Applied to [ 68Ga]Ga-DOTATOC PET/CT in NET Patients Treated with PRRT. Diagnostics (Basel) 2023; 13:diagnostics13040606. [PMID: 36832093 PMCID: PMC9955025 DOI: 10.3390/diagnostics13040606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/28/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND this study aims to explore the prognostic and predictive role of volumetric parameters on [68Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT). METHODS We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [177Lu]Lu-DOTATOC alone or combined with [90Y]Y-DOTATOC. [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board. RESULTS Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups (p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients (p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than -4.17% as well as those with post-SRETV_WB lower than 34.8 cm3 showed a longer PFS (p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS. CONCLUSIONS our results could strengthen the importance of evaluating the burden of disease on [68Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT.
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20
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Konstantinoff KS, Morani AC, Hope TA, Bhosale PR, Francis IR, Yano M, Iravani A, Trikalinos NA, Itani M. Pancreatic neuroendocrine tumors: tailoring imaging to specific clinical scenarios. Abdom Radiol (NY) 2023; 48:1843-1853. [PMID: 36737523 DOI: 10.1007/s00261-022-03737-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 02/05/2023]
Abstract
The clinical and imaging presentation of pancreatic neuroendocrine tumors (PanNETs) is variable and depends on tumor grade, stage, and functional status. This degree of variability combined with a multitude of treatment options and imaging modalities results in complexity when choosing the most appropriate imaging studies across various clinical scenarios. While various guidelines exist in the management and evaluation of PanNETs, there is an overall lack of consensus and detail regarding optimal imaging guidelines and protocols. This manuscript aims to fill gaps where current guidelines may lack specificity regarding the choice of the most appropriate imaging study in the diagnosis, treatment planning, monitoring, and surveillance of PanNETs under various clinical scenarios.
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Affiliation(s)
- Katerina S Konstantinoff
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, The University of California, San Francisco, 185 Berry Street Lobby 6, San Francisco, CA, 94107, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Amir Iravani
- Department of Radiology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Nikolaos A Trikalinos
- Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA.
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21
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Pellegrino F, Granata V, Fusco R, Grassi F, Tafuto S, Perrucci L, Tralli G, Scaglione M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023; 9:217-246. [PMID: 36828370 PMCID: PMC9958666 DOI: 10.3390/tomography9010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
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Affiliation(s)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Francesca Grassi
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Luca Perrucci
- Ferrara Department of Interventional and Diagnostic Radiology, Ospedale di Lagosanto, Azienda AUSL, 44023 Ferrara, Italy
| | - Giulia Tralli
- Department of Radiology, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy
| | - Mariano Scaglione
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
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22
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Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Front Surg 2023; 10:1064145. [PMID: 36950054 PMCID: PMC10025557 DOI: 10.3389/fsurg.2023.1064145] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 02/07/2023] [Indexed: 03/08/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.
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Affiliation(s)
- Apostolos Koffas
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Correspondence: Apostolos Koffas
| | - Alexandros Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Apostolis Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, United Kingdom
| | - Petros Bangeas
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Vasileios N Papadopoulos
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Christos Toumpanakis
- Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom
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23
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Rectal neuroendocrine neoplasms: what the radiologists should know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4016-4031. [PMID: 35288791 DOI: 10.1007/s00261-022-03474-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023]
Abstract
Neuroendocrine neoplasms of the rectum (R-NENs) are rare; however, their incidence has increased almost threefold in the last few decades. Imaging of R-NENs includes two primary categories: anatomic/morphologic imaging comprised of endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and functional/molecular imaging comprising of planar scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). The management depends on stage, dimension, atypical features, histological grade, and lymphovascular invasion (LVI). Low-risk local R-NENs can be resected endoscopically, and high-risk or locally advanced neoplasms can be treated with radical surgery and lymphadenectomy and/or chemoradiation. The review article focuses on imaging illustrations and discusses applications of different imaging modalities in diagnosing and managing R-NENs.
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24
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Lau J, Ioan Cvasciuc T, Simpson D, C de Jong M, Parameswaran R. Continuing challenges of primary neuroendocrine tumours of the thymus: A concisereview. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2360-2368. [PMID: 35922282 DOI: 10.1016/j.ejso.2022.07.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 07/13/2022] [Accepted: 07/18/2022] [Indexed: 12/14/2022]
Abstract
Primary neuroendocrine tumours of the thymus (NETTs) are exceedingly rare tumours, usually presenting around mid-life, which have a propensity towards males and smokers. They are seen more often in those with MEN-1, but multiple different genetic mutations have been found to be involved in the tumorigenesis of NETTs. Histologically, NETTs are classified according to number of mitoses, the presence of necrosis, and the presence or absence of small cell features. NETTs display a wide spectrum of behavior, and they can be incidentally found on chest imaging, on screening in MEN-1, or present with symptoms of local compression. Advanced disease and paraneoplastic syndromes are common. CT-, PET/CT-, MRI-scans, and somatostatin receptor scintigraphy are the imaging modalities of choice both for the initial assessment as well as for monitoring after treatment. For patients with localized disease, complete surgical resection with lymphadenectomy provides the best chance of long-term, disease-free survival, and can be achieved through either an open or thoracoscopic approach. While chemotherapy-regimens based on platinum, taxane, and temozolomide are used most often, the optimum chemotherapy regimen in the adjuvant and palliative settings remains unclear, as does the role of radiotherapy. Ongoing research on the most effective use of somatostatin analogues, peptide receptor radionuclide therapy (PPRT), kinase inhibitors and immunotherapy in patients with other types of advanced neuroendocrine tumours may lead to further treatment options for NETTs in the future.
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Affiliation(s)
- Joel Lau
- Division of Endocrine Surgery, National University Health System, 119074, Singapore
| | - Titus Ioan Cvasciuc
- Division of Endocrine Surgery, Royal Victoria Hospital, Grosvenor Road, Belfast, 274 Grosvenor Rd, Belfast, BT12 6BA, UK
| | - Duncan Simpson
- Division of Endocrine Surgery, Royal Victoria Hospital, Grosvenor Road, Belfast, 274 Grosvenor Rd, Belfast, BT12 6BA, UK
| | - Mechteld C de Jong
- Division of Endocrine Surgery, National University Health System, 119074, Singapore
| | - Rajeev Parameswaran
- Division of Endocrine Surgery, National University Health System, 119074, Singapore; Yong Loo Lin School of Medicine, 10 Medical Dr, 117597, Singapore.
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25
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Delabie P, Baudin É, Hentic O, Afchain P, Rusu T, Montravers F. Diagnostic performance and impact on patient management of [68Ga]Ga-DOTA-TOC PET/CT in colorectal neuroendocrine tumors derived from hindgut. Medicine (Baltimore) 2022; 101:e31512. [PMID: 36451394 PMCID: PMC9704918 DOI: 10.1097/md.0000000000031512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
The main purpose of this retrospective study was to determine the diagnostic performance of [68Ga]Ga-DOTA-D-Phe1-Try3-octreotide(DOTA-TOC) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated colorectal Neuroendocrine Tumours (NETs) originating from the hindgut. The other aims were to assess the impact of the examination on patient management and to analyze the results of 2-[18F]FDG and/or 6-[18F]FDOPA PET/CT when they were performed. [68Ga]Ga-DOTA-TOC PET/CT and clinical data from 30 patients with biopsy-proven well-differentiated NETs originating from the hindgut were retrospectively reviewed and analyzed by comparing the [68Ga]Ga-DOTA-TOC PET/CT findings with pathological and/or follow-up data. We also compared the [68Ga]Ga-DOTA-TOC PET/CT results with 2-[18F]FDG and/or 6-[18F]FDOPA PET/CT results in 6 patients. The impact on management was determined in hindsight by comparing the patient management decided before and after the TEP examination based on data from multidisciplinary team meetings. On a patient basis, [68Ga]Ga-DOTA-TOC PET/CT was accurate in 30 of the 30 examinations. [68Ga]Ga-DOTA-TOC PET/CT correctly identified the primary tumor in all patients with primary tumors not resected before the examination and allowed the detection of unexpected distant metastases in 36% of the patients referred for initial staging. [68Ga]Ga-DOTA-TOC PET/CT findings affected patient management in 57% of cases with generally major intermodality changes. Intraindividual comparison of the results of the different PET radiopharmaceuticals showed a clear superiority of [68Ga]Ga-DOTA-TOC PET/CT considering both the number of lesions and the intensity of uptake. [68Ga]Ga-DOTA-TOC PET/CT is an accurate imaging modality for the assessment of well-differentiated colorectal NETs that highly impact patient management. Thus, we suggest that [68Ga]Ga-DOTA-TOC PET/CT be employed as a first choice for the assessment of these tumors in nuclear medicine.
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Affiliation(s)
- Pierre Delabie
- Department of Nuclear Medicine, Hôpital Tenon AP-HP, Sorbonne Université, Paris, France
| | - Éric Baudin
- Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Villejuif, France
| | - Olivia Hentic
- Department of Gastroenterology and Pancreatology, Hôpital Beaujon AP-HP, Université de Paris, Clichy, France
| | - Pauline Afchain
- Department of Oncology, Hôpital Saint-Antoine AP-HP, Sorbonne Université, Paris, France
| | - Timofei Rusu
- Department of Nuclear Medicine, Hôpital Tenon AP-HP, Sorbonne Université, Paris, France
| | - Françoise Montravers
- Department of Nuclear Medicine, Hôpital Tenon AP-HP, Sorbonne Université, Paris, France
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26
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Poletto G, Cecchin D, Sperti S, Filippi L, Realdon N, Evangelista L. Head-to-Head Comparison between Peptide-Based Radiopharmaceutical for PET and SPECT in the Evaluation of Neuroendocrine Tumors: A Systematic Review. Curr Issues Mol Biol 2022; 44:5516-5530. [PMID: 36354685 PMCID: PMC9689511 DOI: 10.3390/cimb44110373] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 08/04/2023] Open
Abstract
We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68Ga-DOTATOC; 68Ga-DOTATATE; 68Ga-DOTANOC; 99mTc-EDDA/HYNIC-TOC; 64Cu-DOTATATE; and 111In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: "Somatostatin receptor imaging,"; "Somatostatin receptor imaging" and "Functional,"; "Somatostatin receptor imaging" and "SPECT,"; and "Somatostatin receptor imaging" and "PET". Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111In-DTPA-Octreotide and 68Ga-DOTATOC/TATE. Few papers compared 64Cu-DOTATATE and 68Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111In-DTPA-Octreotide, 99mTc-EDDA/HYNIC-TOC, 68Ga-DOTATATE/TOC and 64Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents.
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Affiliation(s)
- Giulia Poletto
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Diego Cecchin
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Stefania Sperti
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
| | - Luca Filippi
- Department of Nuclear Medicine, Santa Maria Goretti Hospital, 04100 Latina, Italy
| | - Nicola Realdon
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy
| | - Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine DIMED, University of Padua, 35128 Padua, Italy
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van Treijen MJC, Korse CM, Verbeek WH, Tesselaar MET, Valk GD. NETest: serial liquid biopsies in gastroenteropancreatic NET surveillance. Endocr Connect 2022; 11:e220146. [PMID: 35951312 PMCID: PMC9513663 DOI: 10.1530/ec-22-0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 11/27/2022]
Abstract
Objective Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied. Design The study was a longitudinal validation study of serial NETest measurements - a blood-based gene expression signature - in 132 patients with GEPNETs on therapy or watch-and-wait strategy. Methods Serial samples were collected during 46 (range: 6-71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED), stable disease (SD) or progressive disease (PD)). Results Consecutive NETest scores fluctuated substantially (range: 0-100) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3-5) and NED subgroups (samples 2-5) compared with baseline results, without changes in imaging. In 82% of untreated patients with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009). Conclusion In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.
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Affiliation(s)
- Mark J C van Treijen
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Catharina M Korse
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Clinical Chemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Wieke H Verbeek
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Gastroenterology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Margot E T Tesselaar
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
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Bentestuen M, Gossili F, Almasi CE, Zacho HD. Prevalence and significance of incidental findings on 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT: a systematic review of the literature. Cancer Imaging 2022; 22:44. [PMID: 36057635 PMCID: PMC9441055 DOI: 10.1186/s40644-022-00484-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Aim We aimed to evaluate the prevalence of incidental 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance in the need for follow-up, and their risk of malignancy. Materials and methods Studies reporting incidental SSTR PET/CT findings were systematically searched in PubMed, Cochrane, Embase and Web of Science literature published prior to 1st of May 2020. Studies were filtered by two independent readers for eligibility based on title and abstract, and subsequently on full text. The main exclusion criteria were: 1) pathological findings that matched scan indication, 2) known organ specific disease and/or incidental findings confirmed on other scan modality prior to SSTR PET/CT, 3) lack of diagnosis and/or follow up, and 4) results published in proceedings or conference abstracts. Results Twenty-one studies, comprising a total of 2906 subjects, were eligible for the analysis. Studies included were retrospective cohort studies on incidental SSTR PET/CT findings in a specific organ (n = 2888, 7/21) or case reports (n = 18, 14/21). A total of 133 subjects had incidental SSTR PET/CT findings. Incidental findings were predominantly seen in the thyroid gland (n = 65), spine (n = 30), brain (n = 26) and breast (n = 6). Seventeen of 133 (13%) incidental findings were malignant on final diagnosis. Incidental breast findings were associated with the highest risk of malignancy (67%). In the thyroid, incidental SSTR uptake was caused by malignancy in 8%, all presenting as focal uptake. The lowest risk was seen in the spine with a malignancy rate of 3% in patients with incidental SSTR uptake and benign cases were interpreted as vertebral hemangiomas on CT. Incidental SSTR PET/CT findings in other locations were of malignant etiology in two out of six cases (33%) and should be evaluated individually. Conclusion The most incidental SSTR PET/CT findings were found in the thyroid gland, spine, and brain. The risk of malignancy was greatest in incidental SSTR PET/CT findings in the breast, cranially, and thyroid gland. The results of the present study can prove useful in the interpretation of atypical findings on SSTR PET/CT and in the counseling of clinicians. Supplementary Information The online version contains supplementary material available at 10.1186/s40644-022-00484-0.
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Affiliation(s)
- Morten Bentestuen
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.
| | - Farid Gossili
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark
| | - Charlotte Elberling Almasi
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark
| | - Helle Damgaard Zacho
- Department of Nuclear Medicine and Clinical Cancer Research Center, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes. Biomaterials 2022; 289:121780. [DOI: 10.1016/j.biomaterials.2022.121780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 07/11/2022] [Accepted: 07/27/2022] [Indexed: 11/18/2022]
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Liu Y, Zhao X, Zhang J, Wang J, Zhang Z, Dai M, Wang N, Jing F, Wang T, Tian W. 68Ga-DOTATATE PET/CT imaging for insulinoma in MEN1 patient with endogenous hyperinsulinemic hypoglycemia: A case report. Medicine (Baltimore) 2022; 101:e30252. [PMID: 36042606 PMCID: PMC9410581 DOI: 10.1097/md.0000000000030252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
RATIONALE Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare and complicated disease that is associated with several endocrine tumors. Here, we report a case of MEN1 associated with insulinoma, parathyroid, and pituitary tumors by 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT). PATIENT CONCERNS A 49-year-old woman presented with intermittent hypoglycemia for more than a year and developed indistinct consciousness without an apparent trigger. DIAGNOSES Biochemical results showed abnormally high serum insulin and parathyroid hormone levels. She underwent an Abdominal magnetic resonance imaging revealed a small nodule in the uncinate process of the pancreas, but it did not clarify the nature of the small nodule. Pituitary magnetic resonance imaging scan revealed a micropituitary tumor, and parathyroid imaging showed no abnormalities. 18F-FDG PET/CT showed no apparent abnormal 18F-FDG uptake in the whole body. In contrast, 68Ga-DOTATATE PET/CT imaging showed pathological radiotracer uptake in the pancreatic uncinate process, accompanied by mild radiotracer uptake in the pituitary gland, and no apparent abnormal radiotracer uptake in the parathyroid area. INTERVENTIONS The patient underwent echoendoscopy for pancreatic uncinate process lesions and surgical resection. OUTCOMES Histological analysis was suggested of insulinoma of pancreatic neuroendocrine tumor, the Ki-67 index was low (only 1% being positive). LESSONS This case demonstrates that 68Ga-DOTATATE can be used for the detection of MEN1-related tumors and preoperative localization of small and low-grade insulinomas by PET/CT.
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Affiliation(s)
- Yunuan Liu
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xinming Zhao
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
- *Correspondence: Xinming Zhao, Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei 050011, China (e-mail: )
| | - Jingmian Zhang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jianfang Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhaoqi Zhang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Meng Dai
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Na Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fenglian Jing
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tingting Wang
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weiwei Tian
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Lutetium-177 DOTATATE: A Practical Review. Pract Radiat Oncol 2022; 12:305-311. [PMID: 35717045 DOI: 10.1016/j.prro.2022.02.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 02/03/2022] [Indexed: 11/21/2022]
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that originate in endocrine tissues throughout the body. Though most are indolent, clinical outcomes vary greatly based on histologic differentiation and grade. Peptide receptor radionuclide therapy has emerged as a promising treatment for patients with locally advanced and/or metastatic disease refractory to standard of care treatment. The phase III NETTER-1 trial found that [177Lu] Lu-DOTA-[Tyr3]-octreotate improved disease-free survival versus octreotide alone for somatostatin receptor-positive gastroenteropancreatic NETs and had a favorable toxicity profile, leading to Food and Drug Administration approval. [177Lu] Lu-DOTA-[Tyr3]-octreotate is an important new treatment that expands the role of radiation in the treatment of NETs. Several important trials are ongoing to better elucidate the role of this treatment.
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Hartrampf P, Werner R, Buck A. Theranostics bei gut bis mäßig differenzierten GEP-NEN. Zentralbl Chir 2022; 147:249-255. [DOI: 10.1055/a-1826-3423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungNeuroendokrine Neoplasien (NEN) sind seltene, heterogene und typischerweise langsam wachsende Tumoren. Die häufigsten Lokalisationen finden sich im gastro-entero-pankreatischen System
(GEP-NEN). NENs werden nach proliferativer Aktivität (Ki-67-Index) eingeteilt (G1–3). Gut differenzierte Tumoren exprimieren dabei typischerweise Somatostatinrezeptoren (SSTR), die als
Zielstruktur in der nuklearmedizinischen Theranostik dienen. Bei diesem Prinzip kann nach einer diagnostischen molekularen Bildgebung, meist mittels
Positronenemissionstomografie/Computertomografie (PET/CT), eine individuell zugeschnittene Peptidradiorezeptortherapie (PRRT) mit einem β-Strahler-markierten Radiopharmakon erfolgen. In
Metaanalysen zeigte die Diagnostik mittels SSTR-gerichteter PET/CT eine Sensitivität von 93% und eine Spezifität von 96%. Die SSTR-gerichtete Diagnostik kann auch zur radioaktiven Markierung
von Tumoren verwendet werden, um eine zielgerichtete Chirurgie zu ermöglichen. Die Indikation zur Einleitung einer PRRT soll stets in einer interdisziplinären Tumorkonferenz getroffen
werden. Ein Tumorprogress unter der vorangegangenen Therapie sollte dokumentiert sein. Die Therapie wird intravenös und insgesamt 4-mal in 8-wöchigem Abstand in spezialisierten
nuklearmedizinischen Zentren verabreicht. Die Wirksamkeit der PRRT wurde in der NETTER-1-Studie prospektiv untersucht und konnte eine signifikante Verbesserung des progressionsfreien
Überlebens (primärer Endpunkt) zeigen. Ausgehend von diesen Studienergebnissen steht mit Lutathera (177Lu-DOTATATE) inzwischen ein in Deutschland zugelassenes Radiopharmazeutikum zu
Behandlung von nicht resektablen oder metastasierten bzw. progredienten, gut differenzierten (G1 und G2), SSTR-positiven GEP-NEN zur Verfügung.
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Affiliation(s)
- Philipp Hartrampf
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Rudolf Werner
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Andreas Buck
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
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Christ E, Wild D, Refardt J. Molecular Imaging in neuroendocrine neoplasias. Presse Med 2022; 51:104115. [PMID: 35131317 DOI: 10.1016/j.lpm.2022.104115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 01/11/2022] [Accepted: 01/28/2022] [Indexed: 12/16/2022] Open
Abstract
Molecular imaging, which uses molecular targets due to the overexpression of specific peptide hormone receptors on the tumour surface, has become an indispensable diagnostic technique. Neuroendocrine neoplasms (NENs) especially differentiated NENs or neuroendocrine tumours (NETs) are a rare group of heterogeneous tumours, characterized by the expression of hormone receptors on the tumour cell surface. This property makes them receptive to diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Amongst the known hormone receptors, somatostatin receptors (SSTR) are expressed on the majority of NETs and are therefore the most relevant receptors for theranostic approaches. Current research aims to medically upregulate their expression, while other focuses are on the use of different radiopeptides (64Cu and 67Cu) or somatostatin-antagonists instead of the established somatostatin agonists. The GLP-1 receptor is another clinically relevant target, as GLP-1-R imaging has become the new standard for the localisation of insulinomas. For staging and prognostic evaluation in dedifferentiated NENs, 18F-FDG-imaging is useful, but lacks a therapeutic counterpart. Further options for patients with insufficient expression of SSTR involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4). New targets such as the glucose-dependant insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs recently and await further evaluation. For medullary thyroid cancer 18-F-DOPA imaging is standard, however this technique is rather second line for other NENs. In this area, the discovery of minigastrin, which targets the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut NENs, may improve future management. This review aims to provide an overview of the most commonly used functional imaging modalities for theranostics in NENs today and in the possible future.
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Affiliation(s)
- Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - Julie Refardt
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland; Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
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34
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Carlsen EA, Lindholm K, Hindsholm A, Gæde M, Ladefoged CN, Loft M, Johnbeck CB, Langer SW, Oturai P, Knigge U, Kjaer A, Andersen FL. A convolutional neural network for total tumor segmentation in [ 64Cu]Cu-DOTATATE PET/CT of patients with neuroendocrine neoplasms. EJNMMI Res 2022; 12:30. [PMID: 35633448 PMCID: PMC9148347 DOI: 10.1186/s13550-022-00901-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/07/2022] [Indexed: 11/24/2022] Open
Abstract
Background Segmentation of neuroendocrine neoplasms (NENs) in [64Cu]Cu-DOTATATE positron emission tomography makes it possible to extract quantitative measures useable for prognostication of patients. However, manual tumor segmentation is cumbersome and time-consuming. Therefore, we aimed to implement and test an artificial intelligence (AI) network for tumor segmentation. Patients with gastroenteropancreatic or lung NEN with [64Cu]Cu-DOTATATE PET/CT performed were included in our training (n = 117) and test cohort (n = 41). Further, 10 patients with no signs of NEN were included as negative controls. Ground truth segmentations were obtained by a standardized semiautomatic method for tumor segmentation by a physician. The nnU-Net framework was used to set up a deep learning U-net architecture. Dice score, sensitivity and precision were used for selection of the final model. AI segmentations were implemented in a clinical imaging viewer where a physician evaluated performance and performed manual adjustments. Results Cross-validation training was used to generate models and an ensemble model. The ensemble model performed best overall with a lesion-wise dice of 0.850 and pixel-wise dice, precision and sensitivity of 0.801, 0.786 and 0.872, respectively. Performance of the ensemble model was acceptable with some degree of manual adjustment in 35/41 (85%) patients. Final tumor segmentation could be obtained from the AI model with manual adjustments in 5 min versus 17 min for ground truth method, p < 0.01. Conclusion We implemented and validated an AI model that achieved a high similarity with ground truth segmentation and resulted in faster tumor segmentation. With AI, total tumor segmentation may become feasible in the clinical routine. Supplementary Information The online version contains supplementary material available at 10.1186/s13550-022-00901-2.
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Affiliation(s)
- Esben Andreas Carlsen
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Kristian Lindholm
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Amalie Hindsholm
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Mathias Gæde
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Claes Nøhr Ladefoged
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Mathias Loft
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Camilla Bardram Johnbeck
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Seppo Wang Langer
- ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Peter Oturai
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Endocrinology and Surgical Gastroenterology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. .,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
| | - Flemming Littrup Andersen
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
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Galgano SJ, Iravani A, Bodei L, El-Haddad G, Hofman MS, Kong G. Imaging of Neuroendocrine Neoplasms: Monitoring Treatment Response- AJR Expert Panel Narrative Review. AJR Am J Roentgenol 2022; 218:767-780. [PMID: 34985313 DOI: 10.2214/ajr.21.27159] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Neuroendocrine neoplasms (NENs) encompass a broad spectrum of tumors throughout the body and range in biologic behavior from indolent to aggressive. Consequently, a wide spectrum of treatment options are available for NENs, including observation, somatostatin analogues, targeted therapy, chemotherapy, surgical resection, liver-directed therapy (embolization and ablation), and peptide receptor radionuclide therapy. Given the wide variety of tumor behaviors and treatments, precise criteria for treatment response in NENs are lacking. Though conventional anatomic imaging with CT and MRI remains important for NEN response assessment, the use of somatostatin receptor (SSR) PET is increasing and often provides synergistic and complementary information. Additionally, in certain clinical scenarios, a particular imaging strategy may prove superior or inferior to others for the detection of metastatic disease and evaluation of therapy response. A strong need exists to further define appropriate and standardized assessment criteria for tumor response and progression in NEN. This article presents the strengths and weaknesses of individual imaging modalities for evaluating NEN therapy response, including conventional anatomic imaging, SSR PET, FDG PET, dual-tracer PET, and PET/MRI. Ongoing challenges and unmet needs in the use of imaging for NEN response evaluation are explored.
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Affiliation(s)
- Samuel J Galgano
- Department of Radiology, University of Alabama at Birmingham, 619 19th St S, JT N325, Birmingham, AL 35249
| | - Amir Iravani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO
| | - Lisa Bodei
- Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, FL
| | - Michael S Hofman
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
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Zhou J, Zhao R, Pan Y, Ju H, Huang X, Jiang Y, Jin J, Zhang Y. The Diagnostic and Grading Accuracy of 68Ga-DOTATATE and 18F-FDG PET/MR for Pancreatic Neuroendocrine Neoplasms. Front Oncol 2022; 12:796391. [PMID: 35273910 PMCID: PMC8901996 DOI: 10.3389/fonc.2022.796391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/25/2022] [Indexed: 11/13/2022] Open
Abstract
Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68Ga-DOTATATE (G-SUVmax) and 18F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades.
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Affiliation(s)
- Jinxin Zhou
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Runze Zhao
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Pan
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huijun Ju
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinyun Huang
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Jiang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiabin Jin
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yifan Zhang
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms. Cancers (Basel) 2022; 14:cancers14051119. [PMID: 35267427 PMCID: PMC8909424 DOI: 10.3390/cancers14051119] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 02/17/2022] [Accepted: 02/21/2022] [Indexed: 02/08/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.
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Ambrosini V, Zanoni L, Filice A, Lamberti G, Argalia G, Fortunati E, Campana D, Versari A, Fanti S. Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors. Cancers (Basel) 2022; 14:1055. [PMID: 35205805 PMCID: PMC8870358 DOI: 10.3390/cancers14041055] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/10/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.
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Affiliation(s)
- Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Lucia Zanoni
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Angelina Filice
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Giulia Argalia
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Emilia Fortunati
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Stefano Fanti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
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Bodei L, Jayaprakasam VS, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2022:933-974. [DOI: 10.1007/978-3-031-05494-5_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Ragab A, Wu J, Ding X, Clark A, Mischen B, Chauhan A, Oates ME, Anthony L, El Khouli R. 68Ga-DOTATATE PET/CT: The Optimum Standardized Uptake Value (SUV) Internal Reference. Acad Radiol 2022; 29:95-106. [PMID: 34756348 DOI: 10.1016/j.acra.2020.08.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 01/01/2023]
Abstract
RATIONALE AND OBJECTIVES Standardized Uptake Value (SUV) is an important semiquantitative measurement used in the clinical and research domains to assess radiopharmaceutical concentration in tumors versus normal organs, but is susceptible to many factors beyond the tumor biological environment. So, the aim of this study is to identify the optimum internal reference among organs with physiological uptake in 68Ga-DOTATATE PET/CT (DOTA PET/CT) scans. MATERIALS AND METHODS This HIPAA-compliant, IRB-approved study with waiver of consent included retrospective imaging review of 180 consecutive patients with neuroendocrine tumors presenting for DOTA PET/CT image acquisition: Ga-68 DOTATATE dose was reported as (0.054 mCi/Kg) scans between September 2018 and May 2019. Mean value of body weight normalized SUV (SUVbw) and lean body mass normalized SUV (SUL) of liver and spleen were measured. Information about the patients and scan characteristics were collected. The paired Grambsch test was used to compare variance among the measured SUVs. Spearman's rank correlation coefficient was used to assess correlation between SUVs and potential patient- and scan-specific confounding factors. RESULTS Variance of SUL was significantly lower than variance of SUVbw in both liver and spleen (p-value < 0.0001). Variances of liver SUVbw and SUL were significantly lower than the corresponding spleen SUVs. Liver SUL showed the lowest variance (3.69% ± 1.25%) among all measured SUVs. CONCLUSION SUL is a more reproducible, less variable, and therefore more reliable quantitative measure in DOTA PET/CT scans, compared SUVbw. Among the available organs with physiological uptake, liver SUL is the optimum internal reference given the liver's larger size and uniform SUL values resulting in lower variability and better reproducibility.
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Affiliation(s)
- Ahmed Ragab
- Yale New Haven Health - Bridgeport Hospital, Bridgeport, Connecticut
| | - Jianrong Wu
- University of Kentucky College of Medicine, Department of Internal Medicine, Division of Cancer Biostatistics, Lexington, Kentucky; University of Kentucky College of Medicine, Markey Cancer Center, Biostatistics and Bioinformatics Shared Resource Facility, Lexington, Kentucky
| | - Xue Ding
- University of Kentucky College of Medicine, Department of Internal Medicine, Division of Cancer Biostatistics, Lexington, Kentucky
| | - Aurela Clark
- University of Kentucky College of Medicine, Department of Radiology, Division of Nuclear Medicine and Molecular imaging, 800 Rose street, Lexington, 40536 KY
| | - Blaine Mischen
- University of Kentucky College of Medicine, Department of Radiology, Division of Nuclear Medicine and Molecular imaging, 800 Rose street, Lexington, 40536 KY
| | - Aman Chauhan
- University of Kentucky College of Medicine, Department of Internal Medicine, Division of Medical Oncology, Lexington, Kentucky; University of Kentucky College of Medicine, Markey Cancer Center, Lexington, Kentucky
| | - M Elizabeth Oates
- University of Kentucky College of Medicine, Department of Radiology, Division of Nuclear Medicine and Molecular imaging, 800 Rose street, Lexington, 40536 KY
| | - Lowell Anthony
- University of Kentucky College of Medicine, Department of Internal Medicine, Division of Medical Oncology, Lexington, Kentucky; University of Kentucky College of Medicine, Markey Cancer Center, Lexington, Kentucky
| | - Riham El Khouli
- University of Kentucky College of Medicine, Department of Radiology, Division of Nuclear Medicine and Molecular imaging, 800 Rose street, Lexington, 40536 KY; University of Kentucky College of Medicine, Markey Cancer Center, Lexington, Kentucky.
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Duan H, Iagaru A, Aparici CM. Radiotheranostics - Precision Medicine in Nuclear Medicine and Molecular Imaging. Nanotheranostics 2022; 6:103-117. [PMID: 34976584 PMCID: PMC8671964 DOI: 10.7150/ntno.64141] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023] Open
Abstract
'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.
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Affiliation(s)
| | | | - Carina Mari Aparici
- Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, Stanford University, Stanford, CA, USA
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Refardt J, Hofland J, Wild D, Christ E. New Directions in Imaging Neuroendocrine Neoplasms. Curr Oncol Rep 2021; 23:143. [PMID: 34735669 PMCID: PMC8568754 DOI: 10.1007/s11912-021-01139-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2021] [Indexed: 12/14/2022]
Abstract
Purpose of Review Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered rapid development in the field. This review aims at giving an overview on contemporary imaging methods and providing an outlook on current progresses. Recent Findings The discovery of molecular targets due to the overexpression of specific peptide hormone receptors on the NEN’s surface has triggered the development of multiple radionuclide imaging modalities. In addition to the established imaging technique of targeting somatostatin receptors, several alternative radioligands have been developed. Targeting the glucagon-like peptide-1 receptor by exendin-4 has a high sensitivity in localizing insulinomas. For dedifferentiated NENs, new molecular targets such as the C-X-C motif chemokine-receptor-4 have been evaluated. Other new targets involve the fibroblast activation protein and the cholecystokinin-2 receptors, where the ligand minigastrin opens new possibilities for the management of medullary thyroid carcinoma. Summary Molecular imaging is an emerging field that improves the management of NENs.
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Affiliation(s)
- Julie Refardt
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands.,ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.,Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Damian Wild
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.,Division of Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Emanuel Christ
- ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. .,Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
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Segaran N, Devine C, Wang M, Ganeshan D. Current update on imaging for pancreatic neuroendocrine neoplasms. World J Clin Oncol 2021; 12:897-911. [PMID: 34733612 PMCID: PMC8546658 DOI: 10.5306/wjco.v12.i10.897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/21/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNEN) are a heterogeneous group of tumors with differing pathological, genetic, and clinical features. Based on clinical findings, they may be categorized into functioning and nonfunctioning tumors. Adoption of the 2017 World Health Organization classification system, particularly its differentiation between grade 3, well-differentiated pancreatic neuroendocrine tumors (panNET) and grade 3, poorly-differentiated pancreatic neuroendocrine carcinomas (panNEC) has emphasized the role imaging plays in characterizing these lesions. Endoscopic ultrasound can help obtain biopsy specimen and assess tumor margins and local spread. Enhancement patterns on computed tomography (CT) and magnetic resonance imaging (MRI) may be used to classify panNEN. Contrast enhanced MRI and diffusion-weighted imaging have been reported to be useful for characterization of panNEN and quantifying metastatic burden. Current and emerging radiotracers have broadened the utility of functional imaging in evaluating panNEN. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT and somatostatin receptor imaging such as Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate PET/CT may be useful for improved identification of panNEN in comparison to anatomic modalities. These new techniques can also play a direct role in optimizing the selection of treatment for individuals and predicting tumor response based on somatostatin receptor expression. In addition, emerging methods of radiomics such as texture analysis may be a potential tool for staging and outcome prediction in panNEN, however further investigation is required before clinical implementation.
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Affiliation(s)
- Nicole Segaran
- Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ 85259, United States
| | - Catherine Devine
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mindy Wang
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Dhakshinamoorthy Ganeshan
- Department of Diagnostic Radiology, Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Treglia G, Sadeghi R, Giovinazzo F, Galiandro F, Annunziata S, Muoio B, Kroiss AS. PET with Different Radiopharmaceuticals in Neuroendocrine Neoplasms: An Umbrella Review of Published Meta-Analyses. Cancers (Basel) 2021; 13:5172. [PMID: 34680321 PMCID: PMC8533943 DOI: 10.3390/cancers13205172] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/03/2021] [Accepted: 10/11/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Several meta-analyses have reported quantitative data about the diagnostic performance, the prognostic value, the impact on management and the safety of positron emission tomography (PET) including related hybrid modalities (PET/CT or PET/MRI) using different radiopharmaceuticals in patients with neuroendocrine neoplasms. We performed an umbrella review of published meta-analyses to provide an evidence-based summary. METHODS A comprehensive literature search of meta-analyses listed in PubMed/MEDLINE and Cochrane Library databases was carried out (last search date: 30 June 2021). RESULTS Thirty-four published meta-analyses were selected and summarized. About the diagnostic performance: 68Ga-SSA PET yields high diagnostic performance in patients with NETs and PGL; 18F-FDOPA PET yields good diagnostic performance in patients with intestinal NETs, PGL, NB, being the best available PET method in detecting rMTC; 68Ga-exendin-4 PET has good diagnostic accuracy in detecting insulinomas; 18F-FDG PET has good diagnostic performance in detecting aggressive neuroendocrine neoplasms. About the prognostic value: 68Ga-SSA PET has a recognized prognostic value in well-differentiated NETs, whereas 18F-FDG PET has a recognized prognostic value in aggressive neuroendocrine neoplasms. A significant clinical impact of 68Ga-SSA PET and related hybrid modalities in patients with NETs was demonstrated. There are no major toxicities or safety issues related to the use of PET radiopharmaceuticals in patients with neuroendocrine neoplasms. CONCLUSIONS Evidence-based data support the use of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms with specific indications for each radiopharmaceutical.
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Affiliation(s)
- Giorgio Treglia
- Clinic of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, 1011 Lausanne, Switzerland
- Academic Education, Research and Innovation Area, General Directorate, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera italiana, 6900 Lugano, Switzerland
| | - Ramin Sadeghi
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad 9919991766, Iran;
| | - Francesco Giovinazzo
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.G.); (F.G.)
| | - Federica Galiandro
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.G.); (F.G.)
| | - Salvatore Annunziata
- UOC Medicina Nucleare, TracerGLab, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Barbara Muoio
- Department of Medicine and Oncology, Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland;
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Iwata M, Sakamoto K, Matsui T, Nishi Y, Nagaoka T, Tamura K, Funamizu N, Takai A, Ogawa K, Kitazawa R, Kitazawa S, Takada Y. Forty-Five Pancreatic Gastrinomas in Multiple Endocrine Neoplasia Type 1: A Case Report. THE JAPANESE JOURNAL OF GASTROENTEROLOGICAL SURGERY 2021; 54:622-629. [DOI: 10.5833/jjgs.2020.0122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- Miku Iwata
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Takashi Matsui
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Yusuke Nishi
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Tomoyuki Nagaoka
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Kei Tamura
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Naotake Funamizu
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Akihiro Takai
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Kohei Ogawa
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
| | - Riko Kitazawa
- Department of Molecular Pathology, Ehime University Graduate School of Medicine
| | - Sohei Kitazawa
- Department of Molecular Pathology, Ehime University Graduate School of Medicine
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine
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Rinke A, Auernhammer CJ, Bodei L, Kidd M, Krug S, Lawlor R, Marinoni I, Perren A, Scarpa A, Sorbye H, Pavel ME, Weber MM, Modlin I, Gress TM. Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine? Gut 2021; 70:1768-1781. [PMID: 33692095 DOI: 10.1136/gutjnl-2020-321300] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 12/14/2022]
Abstract
Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups. Translation of this genomic and mechanistic biology into advanced GEPNEN management is limited. 'Targeted' treatments such as somatostatin analogues, peptide receptor radiotherapy, tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are treatment options but predictive tools are lacking. The inability to identify clonal heterogeneity and define critical oncoregulatory pathways prior to therapy, restrict therapeutic efficacy as does the inability to monitor disease status in real time. Chemotherapy in the poor prognosis NEN G3 group, though associated with acceptable response rates, only leads to short-term tumour control and their molecular biology requires delineation to provide new and more specific treatment options.The future requires an exploration of the NEN tumour genome, its microenvironment and an identification of critical oncologic checkpoints for precise drug targeting. In the advance to personalised medical treatment of patients with GEPNEN, clinical trials need to be based on mechanistic and multidimensional characterisation of each tumour in order to identify the therapeutic agent effective for the individual tumour.This review surveys advances in NEN research and delineates the current status of translation with a view to laying the basis for a genome-based personalised medicine management of advanced GEPNEN.
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Affiliation(s)
- Anja Rinke
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
| | - Christoph J Auernhammer
- Department of Internal Medicine IV and Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Ludwig Maximilian University, LMU Klinikum, Munich, Germany
| | - Lisa Bodei
- Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Mark Kidd
- Wren Laboratories, Branford, Connecticut, USA
| | - Sebastian Krug
- Clinic for Internal Medicine I, Martin Luther University, Halle, Germany
| | - Rita Lawlor
- Applied Research on Cancer Centre, Department of Pathology and Diagnostics, University of Verona, Verona, Italy
| | - Ilaria Marinoni
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Aurel Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Aldo Scarpa
- Applied Research on Cancer Centre, Department of Pathology and Diagnostics, University of Verona, Verona, Italy
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Marianne Ellen Pavel
- Department of Internal Medicine I, Endocrinology, University of Erlangen, Erlangen, Germany
| | - Matthias M Weber
- Department of Internal Medicine I, Endocrinology, Johannes Gutenberg University Hospital Mainz, Mainz, Germany
| | - Irvin Modlin
- Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Thomas M Gress
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
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Abstract
Consensus guidelines acknowledge the role of gallium Ga-68 (68Ga) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA) somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) in management of neuroendocrine tumor (NET) patients. 68Ga-DOTA-SSTR PET/CT demonstrates superior performance to conventional imaging in initial detection, staging, detection of recurrent tumor, and detection of unknown primary in known metastatic disease. 68Ga-DOTA-SSTR PET/CT is low yield for NET detection in the setting of symptoms or elevated biomarkers when conventional imaging is negative, but may still guide management. The role of 68Ga-DOTA-SSTR PET/CT is not established in monitoring response to systemic therapy but may identify progression through detection of new metastases.
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Affiliation(s)
- Janet Pollard
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.
| | - Parren McNeely
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Yusuf Menda
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
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Kong G, Hicks R. Radionuclide imaging of NENs. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 18:207-215. [DOI: 10.1016/j.coemr.2021.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Jawlakh H, Velikyan I, Welin S, Sundin A. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI are superior to 68 Ga-DOTATOC-PET/CT for neuroendocrine tumour imaging. J Neuroendocrinol 2021; 33:e12981. [PMID: 34046974 DOI: 10.1111/jne.12981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/07/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
The present study aimed to assess gadoxetate disodium contrast-enhanced (CE) positron emission tomography (PET)/magnetic resonance imaging (MRI) with 68 Ga-DOTATOC and 11 C-5-Hydroxy-tryptophan (11 C-5-HTP) in comparison with iodine CE 68 Ga-DOTATOC-PET/computed tomography (CT) for neuroendocrine tumour imaging. Detection rate and reader's confidence were evaluated for each separate image volume: CE-CT, CE-MRI including diffusion-weighted imaging, 68 Ga-DOTATOC-PET performed at PET/CT, 68 Ga-DOTATOC-PET performed at PET/MRI and 11 C-5-HTP-PET, and for the three combined hybrid examinations 68 Ga-DOTATOC-PET/MRI, 11 C-5-HTP-PET/MRI and 68 Ga-DOTATOC-PET/CT. In 11 patients, 255 lesions were depicted. 68 Ga-DOTATOC-PET performed at PET/MRI depicted 72.5%, 68 Ga-DOTATOC-PET performed at PET/CT depicted 62.7%, 11 C-5-HTP-PET depicted 68.2% and CE-CT depicted 53% of lesions. 68 Ga-DOTATOC-PET performed at PET/MRI (P < 0.001) and PET/CT (P = 0.02), 11 C-5-HTP-PET (P < 0.001) and MRI (P < 0.001) were superior to CT. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI detected 92.5% and 92% of lesions, respectively, and both outperformed 68 Ga-DOTATOC-PET/CT (65%) (P < 0.001). For liver metastasis imaging, MRI alone was unsurpassed (P < 0.01) and 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI outperformed 68 Ga-DOTATOC-PET/CT (P < 0.001). For lymph node metastasis diagnosis, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET detected 94%, 94% and 94% of lesions, respectively, and outperformed MRI and CE-CT alone (P < 0.001). For bone metastasis imaging, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET performed equally well (P = 0.05) and better than MRI. Reader's confidence was better for 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI than for 68 Ga-DOTATOC-PET/CT. The tumour maximum standardised uptake value and tumour-to-liver ratio were both approximately twice as high as for 68 Ga-DOTATOC than for 11 C-5-HTP. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI provided the highest detection rates and reader's confidence and were both superior to 68 Ga-DOTATOC-PET/CT, mainly because of the MRI component. The imaging contrast with 68 Ga-DOTATOC was superior to that of 11 C-5-HTP.
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Affiliation(s)
- Hiba Jawlakh
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Irina Velikyan
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Anders Sundin
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
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PET findings after COVID-19 vaccination: "Keep Calm and Carry On". Clin Transl Imaging 2021; 9:209-214. [PMID: 34007835 PMCID: PMC8117802 DOI: 10.1007/s40336-021-00430-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/06/2021] [Indexed: 12/18/2022]
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