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Fonseca AI, Sereno J, Almeida S, Ferreira H, Hrynchak I, Falcão A, Alves F, Gomes C, Abrunhosa AJ. Unveiling the potential of copper-61 vs. gallium-68 for SSTR PET imaging. Eur J Nucl Med Mol Imaging 2025:10.1007/s00259-025-07116-2. [PMID: 39909885 DOI: 10.1007/s00259-025-07116-2] [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: 08/05/2024] [Accepted: 01/24/2025] [Indexed: 02/07/2025]
Abstract
PURPOSE In recent years, copper-61 has attracted considerable attention from both physicists and radiochemists due to its favorable physical decay properties for PET imaging and its ease of production at any cyclotron center producing [18F]FDG. The aim of this study was to evaluate the potential of 61Cu-based radiopharmaceuticals for PET imaging of NETs, as an alternative to the commonly used gallium-68. METHODS Copper-61 was produced by irradiation of natural zinc liquid targets, followed by post-processing. In vitro evaluation of 61Cu- and 68Ga-labeled SST analogues was performed in SSTR positive AR42J tumor cells. PET/MRI was carried out in mice bearing AR42J subcutaneous tumors. RESULTS High molar activity [61Cu]Cu-DOTA-TATE and [61Cu]Cu-NOTA-TATE were successfully prepared with a radiochemical purity of over 95% and were shown to be stable for at least 6 h after the EOS. Both 61Cu- and 68Ga-labeled SST analogues exhibited high cellular uptake, with residual uptake when blocked with an excessive amount of peptide precursor. [61Cu]Cu-NOTA-TATE showed the highest tumor uptake at 1 h p.i. (13.25 ± 1.86%ID/g) and the tumor-to-non-tumor ratio increased from 1 h to 4 h p.i. At the later time point, tumor visualization improved compared to 1 h p.i. Moreover, preclinical PET/MR images demonstrated that [61Cu]Cu-NOTA-TATE has a more favorable biodistribution and imaging properties than [61Cu]Cu-DOTA-TATE, with the extended PET imaging window providing a clear advantage of [61Cu]Cu-NOTA-TATE over its gallium-68 analogues. CONCLUSION [61Cu]Cu-NOTA-TATE showed similar biodistribution and pharmacokinetics to [68Ga]Ga-DOTA-TATE at 1 h p.i., while demonstrating superior imaging characteristics for late PET imaging. These findings demonstrate that [61Cu]Cu-NOTA-TATE holds promising characteristics for improving the detection of NETs with increased translational potential.
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Affiliation(s)
- A I Fonseca
- ICNAS Pharma, University of Coimbra, Coimbra, Portugal
| | - J Sereno
- CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal
| | - S Almeida
- ICNAS Pharma, University of Coimbra, Coimbra, Portugal
| | - H Ferreira
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra, Coimbra, Portugal
| | - I Hrynchak
- ICNAS Pharma, University of Coimbra, Coimbra, Portugal
- CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal
| | - A Falcão
- CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - F Alves
- CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal
- ESTeSC - Coimbra Health School, Instituto Politécnico Coimbra, Coimbra, Portugal
| | - C Gomes
- Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology Consortium (CIBB), University of Coimbra, Coimbra, Portugal
| | - A J Abrunhosa
- CIBIT/ICNAS, Institute for Nuclear Science Applied to Health, University of Coimbra, Coimbra, Portugal.
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Pandjarova I, Mercieca D, Gijtenbeek RG, Pereira JO, Fantin A, Castaldo N, Keramida E, Pannu K, Konsoulova A, Aujayeb A. Small cell lung cancer and neuroendocrine tumours. Breathe (Sheff) 2024; 20:240004. [PMID: 39534494 PMCID: PMC11555584 DOI: 10.1183/20734735.0004-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 08/07/2024] [Indexed: 11/16/2024] Open
Abstract
Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.
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Affiliation(s)
| | - Darlene Mercieca
- Department of Respiratory Medicine, Mater Dei Hospital Malta, Triq Dun Karm, Malta
| | - Rolof G.P. Gijtenbeek
- Department of Respiratory Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - João Oliveira Pereira
- Department of Pulmonology, Coimbra Hospital University Centre, Praceta Prof. Mota Pinto, Coimbra, Portugal
| | - Alberto Fantin
- Department of Pulmonology, University Hospital of Udine (ASUFC), Udine, Italy
| | - Nadia Castaldo
- Department of Pulmonology, University Hospital of Udine (ASUFC), Udine, Italy
| | - Elli Keramida
- Sotiria General Hospital of Chest Diseases of Athens, 9th Department of Respiratory Medicine, Athens, Greece
| | - Kanwar Pannu
- Department of Respiratory Medicine, Mid and South Essex NHS Trust, Basildon University Hospital, Basildon, UK
| | - Assia Konsoulova
- National Cancer Hospital, Sofia, Bulgaria
- Women for Oncology, Bulgaria
| | - Avinash Aujayeb
- Department of Respiratory Medicine, Northumbria Healthcare NHS Trust, Cramlington, UK
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Moreau A, Chaouat C, Walter T, Dupré A, Kryza D. False-Negative Neuroendocrine Tumor Identified With 68 Ga-DOTATOC PET/CT : A Case of Well-Differentiated Somatostatinoma. Clin Nucl Med 2024; 49:764-766. [PMID: 38689443 DOI: 10.1097/rlu.0000000000005241] [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: 05/02/2024]
Abstract
ABSTRACT We report the case of a 25-year-old man who was undergoing follow-up for neurofibromatosis type 1. The man underwent 68 Ga-DOTATOC PET/CT for a suspected well-differentiated duodenal neuroendocrine tumor. This examination did not reveal any significant uptake, whereas complementary 18 F-FDG PET/CT showed moderate 18 F-FDG uptake in the primary tumor as well as the adenopathy. Histology, a well-differentiated duodenal neuroendocrine tumor was confirmed, consistent with the diagnosis of somatostatinoma. Although rare, this well-differentiated neuroendocrine tumor should be kept in mind as a possible source of false-negative somatostatin receptor PET/CT findings.
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He Q, Zhang Z, Zhang L, Zhang B, Long Y, Zhang Y, Liao Z, Zha Z, Zhang X. Head-to-head comparison between [ 68Ga]Ga-DOTA-NOC and [ 18F]DOPA PET/CT in a diverse cohort of patients with pheochromocytomas and paragangliomas. Eur J Nucl Med Mol Imaging 2024; 51:1989-2001. [PMID: 38300262 DOI: 10.1007/s00259-024-06622-z] [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] [Received: 12/19/2023] [Accepted: 01/20/2024] [Indexed: 02/02/2024]
Abstract
PURPOSE To compare the detection ability of 68Ga-labelled DOTA-l-Nal3-octreotide ([68Ga]Ga-DOTA-NOC) and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]DOPA) in patients with phaeochromocytomas and paragangliomas (PPGLs) of different origins and gene mutations, such as germline succinate dehydrogenase complex genes (SDHx). METHODS Eighty-five patients with histopathologically confirmed PPGLs who underwent both [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT from March 2017 to June 2023 were enrolled in this retrospective study. For comparative analyses, PPGLs were classified as phaeochromocytoma (PCC), sympathetic paraganglioma (sPGL), and head/neck paraganglioma (HNPGL). Detection rates were analyzed on per-patient and per-lesion bases and compared using the Chi-square/Fischer's exact test. RESULTS Among 85 patients with PPGLs (48 males; 43 years ± 17 [SD]), the patient-based detection rates of [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT were 87.1% (74/85) and 89.4% (76/85), respectively (p = 0.634), and the lesion-based detection rates were 80.8% (479/593) and 71.2% (422/593), respectively (p < 0.001). Only one patient with a recurrent PCC presented double-negative imaging, while 66 patients exhibited double-positive imaging. The remaining patients were either [68Ga]Ga-DOTA-NOC-negative/[18F]DOPA-positive (n = 10) or [68Ga]Ga-DOTA-NOC-positive/[18F]DOPA-negative (n = 8). In subgroup analyses, [68Ga]Ga-DOTA-NOC PET/CT detected significantly more metastases of sPGL (91.1%, 236/259) and SDHx-related PPGL (89.6%, 86/96) than [18F]DOPA PET/CT (48.6%[126/259] and 50.0%[48/96], respectively; both p < 0.001). However, [18F]DOPA showed significantly higher detection rates of PCC in both primary/recurrent and metastatic lesions (94.3%[50/53] vs. 62.3%[33/53] and 87.9%[174/198] vs. 69.2%[137/198], respectively; both p < 0.001). Regarding metastases in different organs, [68Ga]Ga-DOTA-NOC PET/CT detected more lesions than [18F]DOPA PET/CT in bone (96.2%[176/183] vs. 66.1%[121/183]; p < 0.001) and lymph nodes (82.0%[73/89] vs. 53.9%[48/89]; p < 0.001) but less lesions in peritoneum (20%[4/20] vs. 100%[20/20]; p < 0.001). CONCLUSION [68Ga]Ga-DOTA-NOC and [18F]DOPA are complementary in diagnosing PPGL under the appropriate clinical setting. [68Ga]Ga-DOTA-NOC should be considered as the ideal first-line tracer for detecting metastases of sPGL and SDHx-related tumours, whereas [18F]DOPA may be the optimal tracer for evaluating non-SDHx-related PCC, especially in detecting primary lesions and monitoring recurrence.
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Affiliation(s)
- Qiao He
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Zhengkun Zhang
- Department of Urology, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Linqi Zhang
- Department of Nuclear Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong Province, 510095, People's Republic of China
| | - Bing Zhang
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Yali Long
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Yuying Zhang
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Zhihong Liao
- Department of Endocrinology, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China
| | - Zhihao Zha
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China.
| | - Xiangsong Zhang
- Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-Sen University, 58# Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, People's Republic of China.
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Mori H, Tamura M, Ogawa R, Kimata Y, Endo S, Sekine K, Kodama S, Watanabe HH, Ookuma K, Jinzaki M. A Case of Pancreatic Neuroendocrine Tumor with Liver Metastases Demonstrating the Possibility of Enhanced ACTH Production by the SACI Test. Case Rep Endocrinol 2024; 2024:5923680. [PMID: 38681235 PMCID: PMC11055651 DOI: 10.1155/2024/5923680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 03/23/2024] [Accepted: 04/05/2024] [Indexed: 05/01/2024] Open
Abstract
Objective ACTH-producing pancreatic NETs have a propensity to metastasize, and in patients with metastases, there is no established method yet to precisely determine if the excess ACTH is produced by the primary or the metastatic tumors. Localizing the source of production of ACTH in such cases is important for devising suitable treatment strategies and evaluating the benefit of local therapies from the viewpoint of control of Cushing's syndrome. Methods We performed the selective arterial calcium injection (SACI) test combined with selective portal and hepatic venous sampling in a 32-year-old female patient with ectopic ACTH-producing pancreatic NET and liver metastases. Results The blood level of ACTH after Ca loading was significantly elevated only in the vessels thought to be directly feeding the pancreatic tumor, and Ca loading from any artery did not significantly increase ACTH concentrations in the hepatic veins compared to the main trunk of the portal vein. Conclusions The present case demonstrates that there might be an ACTH-producing p-NET that responds to Ca loading. Further in vitro studies are required to validate this possibility.
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Affiliation(s)
- Hirozumi Mori
- Department of Radiology, Saitama City Hospital, Saitama, Japan
| | - Masashi Tamura
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Ryo Ogawa
- Department of Radiology, Saitama City Hospital, Saitama, Japan
| | - Yuta Kimata
- Department of Medicine, Saitama City Hospital, Saitama, Japan
| | - Sho Endo
- Department of Medicine, Saitama City Hospital, Saitama, Japan
| | | | - Sayuri Kodama
- Department of Radiology, Saitama City Hospital, Saitama, Japan
| | | | - Kiyoshi Ookuma
- Department of Radiology, Saitama City Hospital, Saitama, Japan
| | - Masahiro Jinzaki
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
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Lens G, Ahmadi Bidakhvidi N, Vandecaveye V, Grauwels S, Laenen A, Deckers W, Peeters R, Dresen RC, Dekervel J, Verslype C, Nackaerts K, Clement PM, Van Cutsem E, Koole M, Goffin K, Van Laere K, Deroose CM. Intra-individual qualitative and quantitative comparison of [ 68Ga]Ga-DOTATATE PET/CT and PET/MRI. Ther Adv Med Oncol 2023; 15:17588359231189133. [PMID: 37885461 PMCID: PMC10599114 DOI: 10.1177/17588359231189133] [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: 02/27/2023] [Accepted: 07/04/2023] [Indexed: 10/28/2023] Open
Abstract
Background Somatostatin receptor (SSTR) positron emission tomography (PET) is a cornerstone of neuroendocrine tumor (NET) management. Hybrid PET/magnetic resonance imaging (MRI) is now available for NET-imaging, next to PET/computed tomography (CT). Objectives To determine whether CT or MRI is the best hybrid partner for [68Ga]Ga-DOTATATE PET. Design Monocentric, prospective study. Methods Patients received a same-day [68Ga]Ga-DOTATATE PET/CT and subsequent PET/MRI, for suspicion of NET, (re)staging or peptide receptor radionuclide therapy-selection. The union (PETunion) of malignant lesions detected on PETCT and PETMRI was the reference standard. Concordance of detection of malignant lesions in an organ was measured between PETunion and CT and PETunion and MRI. Seven bins were used to categorize the number of malignant lesions, containing following ordinal variables: 0, 1, 2-5, 6-10, 11-20, >20 countable and diffuse/uncountable. The difference in number of malignant lesions was obtained as the difference in bin level ('Δbin') between PETunion and CT and PETunion and MRI with a Δbin closer to zero implying a higher concordance rate. Results Twenty-nine patients were included. Primary tumors included 17 gastroenteropancreatic-NETs, 1 colon neuroendocrine carcinoma, 7 lung-NETs and 2 meningiomas. Patient level concordance with PETunion was 96% for MRI and 67% for CT (p = 0.039). Organ level concordance with PETunion was 74% for MRI and 40% for CT (p < 0.0001). In bone, there was a higher concordance rate for MRI compared to CT, 92% and 33%, respectively (p = 0.016). Overall, a mean Δbin of 0.5 ± 1.1 for PETunion/MRI and 1.4 ± 1.2 for PETunion/CT (p < 0.0001) was noted. In liver, a mean Δbin of 0.0 ± 1.1 for PETunion/MRI and 1.7 ± 1.2 for PETunion/CT was observed (p = 0.0078). In bone, a mean Δbin closer to zero was observed for PETunion/MRI compared to PETunion/CT, 0.6 ± 1.4 and 2.0 ± 1.5, respectively (p = 0.0098). Conclusions Compared to SSTR PET/CT, SSTR PET/MRI had a higher patient and organ level concordance for malignant tumoral involvement and number of malignant lesions, with a clear added value in bone and liver specifically.
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Affiliation(s)
- Géraldine Lens
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Niloefar Ahmadi Bidakhvidi
- Nuclear Medicine, University Hospitals Leuven, Leuven, BelgiumNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | | | | | - Annouschka Laenen
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Leuven, Belgium
| | - Wies Deckers
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | | | | | - Jeroen Dekervel
- Digestive Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Chris Verslype
- Digestive Oncology, University Hospitals Leuven, Leuven, Belgium
| | | | - Paul M. Clement
- General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Michel Koole
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Karolien Goffin
- Nuclear Medicine, University Hospitals Leuven, Leuven, BelgiumNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Koen Van Laere
- Nuclear Medicine, University Hospitals Leuven, Leuven, BelgiumNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Christophe M. Deroose
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Herestraat 49, 3000 Leuven, Flanders, Belgium
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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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Passhak M, McNamara MG, Hubner RA, Ben-Aharon I, Valle JW. Choosing the best systemic treatment sequence for control of tumour growth in gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): What is the recent evidence? Best Pract Res Clin Endocrinol Metab 2023; 37:101836. [PMID: 37914565 DOI: 10.1016/j.beem.2023.101836] [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: 11/03/2023]
Abstract
Gastro-enteropancreatic neuroendocrine tumours (GEP-NETs) represent a rare and highly heterogeneous entity with increasing incidence. Based on the results obtained from several trials performed in the last decade, various therapeutic options have been established for the treatment of patients with GEP-NETs. The options include somatostatin analogues, targeted therapies (sunitinib and everolimus), chemotherapy (with temozolomide or streptozocin-based regimens), and peptide receptor radionuclide therapy. The treatment choice is influenced by various clinico-pathological factors including tumour grade and morphology, the primary mass location, hormone secretion, the volume of the disease and the rate of tumour growth, as well as patient comorbidities and performance status. In this review, the efficacy and safety of treatment options for patients with GEP-NETs is discussed and the evidence to inform the best sequence of available therapies to control tumour growth, prolong patient survival, and to lower potential toxicity, while maintaining patient quality of life is explored.
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Affiliation(s)
- Maria Passhak
- Fishman Oncology Center, Rambam Health Care Campus, Haifa, Israel
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Richard A Hubner
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Irit Ben-Aharon
- Fishman Oncology Center, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
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Wikberg E, van Essen M, Rydén T, Svensson J, Gjertsson P, Bernhardt P. Evaluation of reconstruction methods and image noise levels concerning visual assessment of simulated liver lesions in 111In-octreotide SPECT imaging. EJNMMI Phys 2023; 10:36. [PMID: 37266738 DOI: 10.1186/s40658-023-00557-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 05/15/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND Early cancer detection is crucial for patients' survival. The image quality in 111In-octreotide SPECT imaging could be improved by using Monte Carlo (MC)-based reconstruction. The aim of this observational study was to determine the detection rate of simulated liver lesions for MC-based ordered subset expectation maximization (OSEM) reconstruction compared to conventional attenuation-corrected OSEM reconstruction. METHODS Thirty-seven SPECT/CT examinations with 111In-octreotide were randomly selected. The inclusion criterion was no liver lesions at the time of examination and for the following 3 years. SPECT images of spheres representing lesions were simulated using MC. The raw data of the spheres were added to the raw data of the established healthy patients in 26 of the examinations, and the remaining 11 examinations were not modified. The images were reconstructed using conventional OSEM reconstruction with attenuation correction and post filtering (fAC OSEM) and MC-based OSEM reconstruction without and with post filtering (MC OSEM and fMC OSEM, respectively). The images were visually and blindly evaluated by a nuclear medicine specialist. The criteria evaluated were liver lesion yes or no, including coordinates if yes, with confidence level 1-3. The percentage of detected lesions and accuracy (percentage of correctly classified cases), as well as tumor-to-normal tissue concentration (TNC) ratios and signal-to-noise ratios (SNRs), were evaluated. RESULTS The detection rates were 30.8% for fAC OSEM, 42.3% for fMC OSEM, and 50.0% for MC OSEM. The accuracies were 45.9% for fAC OSEM, 45.9% for fMC OSEM, and 54.1% for MC OSEM. The number of false positives was higher for fMC and MC OSEM. The observer's confidence level was higher in filtered images than in unfiltered images. TNC ratios were significantly higher, statistically, with MC OSEM and fMC OSEM than with AC OSEM, but SNRs were similar due to higher noise with MC OSEM. CONCLUSION One in two lesions were found using MC OSEM versus one in three using conventional reconstruction. TNC ratios were significantly improved, statistically, using MC-based reconstruction, but the noise levels increased and consequently the confidence level of the observer decreased. For further improvements, image noise needs to be suppressed.
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Affiliation(s)
- Emma Wikberg
- Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden.
| | - Martijn van Essen
- Department of Clinical Physiology, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Tobias Rydén
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Johanna Svensson
- Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Peter Gjertsson
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Clinical Physiology, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Peter Bernhardt
- Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
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10
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Prosperi D, Carideo L, Russo VM, Meucci R, Campagna G, Lastoria S, Signore A. A Systematic Review on Combined [ 18F]FDG and 68Ga-SSA PET/CT in Pulmonary Carcinoid. J Clin Med 2023; 12:jcm12113719. [PMID: 37297914 DOI: 10.3390/jcm12113719] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/20/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023] Open
Abstract
Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical carcinoid (AC). TC differ from AC not only for its histopathological features but also for its "functional imaging pattern" and prognosis. ACs are more undifferentiated and characterized by higher aggressiveness. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSA) labeled with Gallium-68 (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE) has widely replaced conventional imaging with gamma camera using 111In- or 99mTc-labelled compounds and represents now the gold standard for diagnosis and management of NENs. In this setting, as already described for gastro-entero-pancreatic NENs, 18F-Fluorodeoxiglucose ([18F]FDG) in addition to 68Ga-SSA can play an important role in clinical practice, particularly for ACs that show a more aggressive behavior compared to TCs. The aim of this systematic review is to analyze all original studies collected from the PubMed and Scopus databases regarding PCs in which both 68Ga-SSA PET/CT and [18F]FDG PET/CT were performed in order to evaluate the clinical impact of each imaging modality. The following keywords were used for the research: "18F, 68Ga and (bronchial carcinoid or carcinoid lung)". A total of 57 papers were found, of which 17 were duplicates, 8 were reviews, 10 were case reports, and 1 was an editorial. Of the remaining 21 papers, 12 were ineligible because they did not focus on PC or did not compare 68Ga-SSA and [18F]FDG. We finally retrieved and analyzed nine papers (245 patients with TCs and 110 patients with ACs), and the results highlight the importance of the combined use of 68Ga-SSA and [18F]FDG PET/CT for the correct management of these neoplasms.
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Affiliation(s)
- Daniela Prosperi
- Nuclear Medicine Unit, University Hospital Sant'Andrea, Via di Grottarossa 1035, 00189 Rome, Italy
| | - Luciano Carideo
- Nuclear Medicine Unit, IRCCS National Cancer Institute, Fondazione Senatore G. Pascale, 80127 Naples, Italy
| | - Vincenzo Marcello Russo
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University, 00184 Rome, Italy
| | - Rosaria Meucci
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University, 00184 Rome, Italy
- U.O.C. Diagnostic Imaging, PTV Policlinico "Tor Vergata" University, Viale Oxford 81, 00133 Rome, Italy
| | - Giuseppe Campagna
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University, 00184 Rome, Italy
| | - Secondo Lastoria
- Nuclear Medicine Unit, IRCCS National Cancer Institute, Fondazione Senatore G. Pascale, 80127 Naples, Italy
| | - Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University, 00184 Rome, Italy
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11
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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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12
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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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13
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Refardt J, Hofland J, Wild D, Christ E. Molecular Imaging of Neuroendocrine Neoplasms. J Clin Endocrinol Metab 2022; 107:e2662-e2670. [PMID: 35380158 DOI: 10.1210/clinem/dgac207] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Indexed: 12/17/2022]
Abstract
The key for molecular imaging is the use of a radiotracer with a radioactive and a functional component. While the functional component targets a specific feature of the tumor, the radioactive component makes the target visible. Neuroendocrine neoplasms (NEN) are a diverse group of rare tumors that arise from neuroendocrine cells found mainly in the gastroenteropancreatic system, lung, thyroid, and adrenal glands. They are characterized by the expression of specific hormone receptors on the tumor cell surface, which makes them ideal targets for radiolabeled peptides. The most commonly expressed hormone receptors on NEN cells are the somatostatin receptors. They can be targeted for molecular imaging with various radiolabeled somatostatin analogs, but also with somatostatin antagonists, which have shown improved imaging quality. 18F-DOPA imaging has become a second-line imaging modality in NENs, with the exception of the evaluation of advanced medullary thyroid carcinoma. Alternatives for NENs with insufficient somatostatin receptor expression due to poor differentiation involve targeting glucose metabolism, which can also be used for prognosis. For the localization of the often-small insulinoma, glucagon-like peptide-1 (GLP-1) receptor imaging has become the new standard. Other alternatives involve metaiodobenzylguanidine and the molecular target C-X-C motif chemokine receptor-4. In addition, new radiopeptides targeting the fibroblast activation protein, the glucose-dependent insulinotropic polypeptide receptor and cholecystokinin-2 receptors have been identified in NENs and await further evaluation. This mini-review aims to provide an overview of the major molecular imaging modalities currently used in the field of NENs, and also to provide an outlook on future developments.
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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, Basel, Switzerland
- Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, 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, Basel, Switzerland
- Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - 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
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14
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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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15
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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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16
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Canakis A, Lee LS. Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Endosc 2022; 14:267-290. [PMID: 35719897 PMCID: PMC9157694 DOI: 10.4253/wjge.v14.i5.267] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/14/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.
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Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
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17
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Deleu AL, Laenen A, Decaluwé H, Weynand B, Dooms C, De Wever W, Jentjens S, Goffin K, Vansteenkiste J, Van Laere K, De Leyn P, Nackaerts K, Deroose CM. Value of [ 68Ga]Ga-somatostatin receptor PET/CT in the grading of pulmonary neuroendocrine (carcinoid) tumours and the detection of disseminated disease: single-centre pathology-based analysis and review of the literature. EJNMMI Res 2022; 12:28. [PMID: 35524900 PMCID: PMC9079198 DOI: 10.1186/s13550-022-00900-3] [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: 01/26/2022] [Accepted: 04/25/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [18F]FDG PET/CT in a subgroup of patients. METHODS SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [18F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUVmax) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUVmax values were related to the tumour type (TC versus AC) for both SSTR and [18F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUVmax values were compared to the pathological status (N+ versus N-) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed. RESULTS A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [18F]FDG PET/CT was available in 46 patients. Analysis of the SUVmax values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUVmax 18.4 vs 3.8; p = 0.003) and significantly higher [18F]FDG uptake in AC compared to TC (median SUVmax 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [18F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[18F]FDG SUVmax values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [18F]FDG PET/CT (difference 0.17; 95% confidence interval - 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed. CONCLUSION Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [18F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.
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Affiliation(s)
- Anne-Leen Deleu
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - Annouschka Laenen
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Louvain, Belgium
| | | | - Birgit Weynand
- Pathology, University Hospitals Leuven, Louvain, Belgium
| | - Christophe Dooms
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | | | - Sander Jentjens
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - Karolien Goffin
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium
| | - Johan Vansteenkiste
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | - Koen Van Laere
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium
| | - Paul De Leyn
- Thoracic Surgery, University Hospitals Leuven, Louvain, Belgium
| | - Kristiaan Nackaerts
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | - Christophe M Deroose
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium.
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium.
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18
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Moreau PL, Aveline C, Christin-Maitre S, Chanson P, Dubreuil O, Rusu T, Montravers F. Role of 68Ga-DOTATOC PET/CT in Insulinoma According to 3 Different Contexts: A Retrospective Study. Clin Nucl Med 2022; 47:394-401. [PMID: 35307723 DOI: 10.1097/rlu.0000000000004126] [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: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to assess the performance of 68Ga-DOTATOC PET/CT in the detection and extension of insulinomas according to 3 different contexts: sporadic benign, sporadic metastatic, and multiple endocrine neoplasia type 1 (MEN1). PATIENTS AND METHODS The data of 71 adult patients who underwent 68Ga-DOTATOC PET/CT for suspected or confirmed sporadic insulinoma, suspicion of insulinoma in the context of MEN1, follow-up of metastatic insulinoma, or suspicion of recurrence of insulinoma were retrospectively analyzed. Pathological examination or strong clinical and biological findings were used as standards of truth. RESULTS For the assessment of a confirmed sporadic insulinoma in 17 patients, the sensitivity of SR-PET was 75%, including 2 patients for whom metastatic lesions had been revealed by SR-PET. For 35 patients with a suspicion of insulinoma, the sensitivity was 39%. In 10 patients followed up for metastatic insulinoma, the sensitivity was 100%. For 5 patients with a history of MEN1, interpretation of SR-PET was difficult, as 3 of them presented with multiple pancreatic uptake foci. The global sensitivity of SR-PET in all insulinomas excluding those with a MEN1 story was 64% (100% for metastatic insulinomas, 62% for benign insulinomas), with a specificity of 89%. CONCLUSIONS 68Ga-DOTATOC PET/CT is a useful examination tool for the assessment of insulinomas in selected contexts, with very high performance for the detection and extension workup of metastatic insulinomas and high specificity for the detection of sporadic benign insulinomas. The examination should be completed with GLP-1 receptor PET when it is negative or in a MEN1 context.
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Affiliation(s)
- Pierre-Louis Moreau
- From the Service de Médecine Nucléaire, Hôpital Tenon AP-HP and Sorbonne University
| | - Cyrielle Aveline
- From the Service de Médecine Nucléaire, Hôpital Tenon AP-HP and Sorbonne University
| | | | - Philippe Chanson
- Endocrinology, Hôpital Bicêtre AP-HP and University Paris Sud, Le Kremlin-Bicêtre
| | - Olivier Dubreuil
- Department of Digestive Oncology, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France
| | - Timofei Rusu
- From the Service de Médecine Nucléaire, Hôpital Tenon AP-HP and Sorbonne University
| | - Françoise Montravers
- From the Service de Médecine Nucléaire, Hôpital Tenon AP-HP and Sorbonne University
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19
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Ichikawa Y, Kobayashi N, Takano S, Kato I, Endo K, Inoue T. Net theranostics. Cancer Sci 2022; 113:1930-1938. [PMID: 35271754 PMCID: PMC9207370 DOI: 10.1111/cas.15327] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 02/17/2022] [Accepted: 03/03/2022] [Indexed: 11/30/2022] Open
Abstract
Theranostics is a term coined by combining the words “therapeutics” and “diagnostics,” referring to single chemical entities developed to deliver therapy and diagnosis simultaneously. Neuroendocrine tumors are rare cancers that occur in various organs of the body, and they express neuroendocrine factors such as chromogranin A and somatostatin receptor. Somatostatin analogs bind to somatostatin receptor, and when combined with diagnostic radionuclides, such as gamma‐emitters, are utilized for diagnosis of neuroendocrine tumor. Somatostatin receptor scintigraphy when combined with therapeutic radionuclides, such as beta‐emitters, are effective in treating neuroendocrine tumor as peptide receptor radionuclide therapy. Somatostatin receptor scintigraphy and peptide receptor radionuclide therapy are some of the most frequently used and successful theranostics for neuroendocrine tumor. In Japan, radiopharmaceuticals are regulated under a complex law system, creating a significant drug lag, which is a major public concern. It took nearly 10 years to obtain the approval for somatostatin receptor scintigraphy and peptide receptor radionuclide therapy use by the Japanese government. In 2021, 111Lu‐DOTATATE (Lutathera), a drug for peptide receptor radionuclide therapy, was covered by insurance in Japan. In this review, we summarize the history of the development of neuroendocrine tumor theranostics and theranostics in general, as therapeutic treatment for cancer in the future. Furthermore, we briefly address the Japanese point of view regarding the development of new radiopharmaceuticals.
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Affiliation(s)
- Yasushi Ichikawa
- Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Shoko Takano
- Department of Radiation Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ikuma Kato
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Keigo Endo
- Kyoto College of Medical Science, Kyoto, Japan
| | - Tomio Inoue
- Department of Radiation Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.,Shonan Kamakura General Hospital, Kamakura, Japan
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20
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Kaewput C, Vinjamuri S. Role of Combined 68Ga DOTA-Peptides and 18F FDG PET/CT in the Evaluation of Gastroenteropancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2022; 12:diagnostics12020280. [PMID: 35204371 PMCID: PMC8871217 DOI: 10.3390/diagnostics12020280] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 12/12/2022] Open
Abstract
This review article summarizes the role of combined 68Ga DOTA-peptides and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Patients with GEP-NENs can initially present themselves to a gastroenterologist or endocrinologist rather than cancer specialist; hence, it is vital for a wider group of clinicians to be familiar with the range of tests available for the evaluation of these patients. The role of PET scanning by using 68Ga DOTA-peptides has a high sensitivity in the diagnosis of GEP-NENs and to guide patient selection for treatment with somatostatin analogues (SSA) and/or peptide receptor radionuclide therapy (PRRT). The loss of somatostatin receptor (SSTR) expression was found to be associated with an increased glucose metabolism in cells. However, the routine use of SSTR targeted radiotracers in combination with 18F-FDG to evaluate glucose utilization in GEP-NENs is still debatable. In our opinion, in patients with NENs, 18F-FDG PET should be performed in the case of a negative or slightly positive 68Ga DOTA-peptides PET scan for assessing the dedifferentiation status, to guide correct therapeutic strategy and to evaluate the prognosis. The approach of combined receptor and metabolic imaging can improve diagnostic accuracy, especially considering the heterogeneity of these lesions. Therefore, 68Ga DOTA-peptides and 18F-FDG PET should be considered complementary in patients with GEP-NENs.
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Affiliation(s)
- Chalermrat Kaewput
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Correspondence: ; Tel.: +66-2419-6220
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool L7 8XP, UK;
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21
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Haslerud T. SPECT/CT in Neuroendrocrine Tumours. CLINICAL APPLICATIONS OF SPECT-CT 2022:95-118. [DOI: 10.1007/978-3-030-65850-2_6] [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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22
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Wagemans ME, Braat AJ, Smits ML, Bruijnen RC, Lam MG. Nuclear medicine therapy of liver metastasis with radiolabelled spheres. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00178-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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23
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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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24
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Wikberg E, van Essen M, Rydén T, Svensson J, Gjertsson P, Bernhardt P. EVALUATION OF THE SPATIAL RESOLUTION IN MONTE CARLO-BASED SPECT/CT RECONSTRUCTION OF 111IN-OCTREOTIDE IMAGES. RADIATION PROTECTION DOSIMETRY 2021; 195:319-326. [PMID: 33885133 PMCID: PMC8507452 DOI: 10.1093/rpd/ncab055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 02/23/2021] [Accepted: 03/30/2021] [Indexed: 06/03/2023]
Abstract
The purpose was to evaluate the spatial resolution in 111In-octreotide single-photom emission computed tomography (SPECT)/computed tomography (CT) imaging following reconstructions with three different ordered subset expectation maximizations (OSEM) reconstruction algorithms; attenuation corrected (AC) OSEM, AC OSEM with resolution recovery (ACRR OSEM) and Monte Carlo-based OSEM reconstruction (MC OSEM). SPECT/CT imaging of a triple line phantom containing 111In in air and water was performed. The spatial resolution, represented by the full width at half maximum (FWHM) of a line profile, was determined for each line, for X and Y direction and for all reconstructions. The mean FWHM was 12.2 mm (±standard deviation [SD] 3.7 mm) for AC OSEM, 9.3 mm (±SD 2.5 mm) for ACRR OSEM and 8.2 mm (±SD 2.0 mm) for MC OSEM. MC-based SPECT/CT reconstruction clearly improves the spatial resolution in 111In-octreotide imaging and since MC simulations can be performed for all photon energies MC OSEM has the potential to improve SPECT/CT imaging overall.
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Affiliation(s)
- Emma Wikberg
- Department of Medical Radiation Sciences, Sahlgrenska Academy, Gothenburg University, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Martijn van Essen
- Department of Clinical Physiology, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Tobias Rydén
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Johanna Svensson
- Department of Oncology, Sahlgrenska Academy, Gothenburg University, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Peter Gjertsson
- Department of Clinical Physiology, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
| | - Peter Bernhardt
- Department of Medical Radiation Sciences, Sahlgrenska Academy, Gothenburg University, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
- Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
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25
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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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26
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Imaging of Pancreatic Neuroendocrine Neoplasms. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18178895. [PMID: 34501485 PMCID: PMC8430610 DOI: 10.3390/ijerph18178895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/16/2021] [Accepted: 08/22/2021] [Indexed: 12/25/2022]
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) represent the second most common pancreatic tumors. They are a heterogeneous group of neoplasms with varying clinical expression and biological behavior, from indolent to aggressive ones. PanNENs can be functioning or non-functioning in accordance with their ability or not to produce metabolically active hormones. They are histopathologically classified according to the 2017 World Health Organization (WHO) classification system. Although the final diagnosis of neuroendocrine tumor relies on histologic examination of biopsy or surgical specimens, both morphologic and functional imaging are crucial for patient care. Morphologic imaging with ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) is used for initial evaluation and staging of disease, as well as surveillance and therapy monitoring. Functional imaging techniques with somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) are used for functional and metabolic assessment that is helpful for therapy management and post-therapeutic re-staging. This article reviews the morphological and functional imaging modalities now available and the imaging features of panNENs. Finally, future imaging challenges, such as radiomics analysis, are illustrated.
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27
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Abstract
Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.
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28
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Draulans C, Pos F, Smeenk RJ, Kerkmeijer L, Vogel WV, Nagarajah J, Janssen M, Mai C, Heijmink S, van der Leest M, Zámecnik P, Oyen R, Isebaert S, Maes F, Joniau S, Kunze-Busch M, De Roover R, Defraene G, van der Heide UA, Goffin K, Haustermans K. 68Ga-PSMA-11 PET, 18F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability. Pract Radiat Oncol 2021; 11:202-211. [PMID: 33941347 DOI: 10.1016/j.prro.2020.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 10/11/2020] [Accepted: 11/08/2020] [Indexed: 02/03/2023]
Abstract
PURPOSE To assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer. METHODS Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used. RESULTS A significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found. CONCLUSIONS Both MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.
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Affiliation(s)
- Cédric Draulans
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium
| | - Floris Pos
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Robert J Smeenk
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Linda Kerkmeijer
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiation Oncology, University Medical Centre, Utrecht, The Netherlands
| | - Wouter V Vogel
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - James Nagarajah
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Marcel Janssen
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Cindy Mai
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Stijn Heijmink
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marloes van der Leest
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Patrik Zámecnik
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Raymond Oyen
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Sofie Isebaert
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium
| | - Frederik Maes
- Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium; Medical Imaging Research Centre, University Hospitals Leuven, Leuven, Belgium
| | - Steven Joniau
- Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Martina Kunze-Busch
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Robin De Roover
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium
| | - Gilles Defraene
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium
| | - Uulke A van der Heide
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Karolien Goffin
- Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Karin Haustermans
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
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Søreide JA, Kvaløy JT, Lea D, Sandvik OM, Al-Saiddi M, Haslerud TM, Garresori H, Karlsen LN, Gudlaugsson E, Søreide K. The overriding role of surgery and tumor grade for long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based cohort study. Cancer Rep (Hoboken) 2021; 5:e1462. [PMID: 34105314 PMCID: PMC8842708 DOI: 10.1002/cnr2.1462] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/26/2021] [Accepted: 05/12/2021] [Indexed: 12/13/2022] Open
Abstract
Background Gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) comprise a heterogeneous disease group. Factors that affect long‐term survival remain uncertain. Complete population‐representative cohorts with long‐term follow‐up are scarce. Aim To evaluate factors of importance for the long‐term survival. Methods and results An Observational population‐based study on consecutive GEP‐NEN patients diagnosed from 2003 to 2013, managed according to national guidelines. Univariable and multivariable survival analyses were performed to evaluate overall survival (OS) and to identify independent prognostic factors. One hundred ninety eligible patients (males, 58.9%) (median age, 60.0 years; range, 10.0–94.2 years) were included. The small bowel, appendix, and pancreas were the most common tumor locations. The World Health Organization (WHO) tumor grade 1–3 distributions varied according to the primary location and disease stage. Primary surgery with curative intent was performed in 66% of the patients. The median OS of the study population was 183 months with 5‐ and 10‐year OS rates of 66% and 57%, respectively. Only age, WHO tumor grade, and primary surgical treatment were independent prognostic factors for OS. Conclusion The outcomes of GEP‐NEN patients are related to several factors including age and primary surgical treatment. WHO tumor grading, based on the established criteria, should be routine in clinical practice. This may improve clinical decision‐making and allow the comparison of outcomes among different centers.
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Affiliation(s)
- Jon Arne Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Jan Terje Kvaløy
- Department of Research, Stavanger University Hospital, Stavanger, Norway.,Department of Mathematics and Physics, University of Stavanger, Stavanger, Norway
| | - Dordi Lea
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Pathology, Stavanger University Hospital, Stavanger, Norway
| | - Oddvar M Sandvik
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Mohammed Al-Saiddi
- Department of Radiology and Nuclear Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Torjan M Haslerud
- Department of Radiology and Nuclear Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Herish Garresori
- Department of Oncology, Stavanger University Hospital, Stavanger, Norway
| | - Lars N Karlsen
- Department of Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Einar Gudlaugsson
- Department of Pathology, Stavanger University Hospital, Stavanger, Norway
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
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30
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Collamati F, van Oosterom MN, Hadaschik BA, Fragoso Costa P, Darr C. Beta radioguided surgery: towards routine implementation? THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2021; 65:229-243. [PMID: 34014062 DOI: 10.23736/s1824-4785.21.03358-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases. Reliable intraoperative detection of small cancerous tissue would allow surgeons to selectively resect malignant areas: this task can be achieved by means of image-guided surgery, such as beta radioguided surgery (RGS). EVIDENCE ACQUISITION In this paper, a comprehensive review of beta RGS is given, starting from the physical principles that differentiate beta from gamma radiation, that has already its place in nuclear medicine current practice. Also, the recent clinical feasibility of using Cerenkov radiation is discussed. EVIDENCE SYNTHESIS Despite being first proposed several decades ago, only in the last years a remarkable interest in beta RGS has been observed, probably driven by the diffusion of PET radio tracers. Today several different approaches are being pursued to assess the effectiveness of such a technique, including both beta+ and beta- emitting radiopharmaceuticals. CONCLUSIONS Beta RGS shows some peculiarities that can present it as a very promising complementary technique to standard procedures. Good results are being obtained in several tests, both ex vivo and in vivo. This might however be the time to initiate the trials to demonstrate the real clinical value of these technologies with seemingly clear potential.
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Affiliation(s)
| | - Matthias N van Oosterom
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.,Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Boris A Hadaschik
- Department of Urology, University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Pedro Fragoso Costa
- German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.,Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
| | - Christopher Darr
- Department of Urology, University Hospital Essen, Essen, Germany.,German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
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Hu Y, Ye Z, Wang F, Qin Y, Xu X, Yu X, Ji S. Role of Somatostatin Receptor in Pancreatic Neuroendocrine Tumor Development, Diagnosis, and Therapy. Front Endocrinol (Lausanne) 2021; 12:679000. [PMID: 34093445 PMCID: PMC8170475 DOI: 10.3389/fendo.2021.679000] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/27/2021] [Indexed: 12/02/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare and part of the diverse family of neuroendocrine neoplasms (NENs). Somatostatin receptors (SSTRs), which are widely expressed in NENs, are G-protein coupled receptors that can be activated by somatostatins or its synthetic analogs. Therefore, SSTRs have been widely researched as a diagnostic marker and therapeutic target in pNETs. A large number of studies have demonstrated the clinical significance of SSTRs in pNETs. In this review, relevant literature has been appraised to summarize the most recent empirical evidence addressing the clinical significance of SSTRs in pNETs. Overall, these studies have shown that SSTRs have great value in the diagnosis, treatment, and prognostic prediction of pNETs; however, further research is still necessary.
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Affiliation(s)
- Yuheng Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zeng Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Fei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Sahnoun S, Conen P, Mottaghy FM. The battle on time, money and precision: Da[ 18F] id vs. [ 68Ga]liath. Eur J Nucl Med Mol Imaging 2021; 47:2944-2946. [PMID: 32715336 PMCID: PMC7680323 DOI: 10.1007/s00259-020-04961-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- Sabri Sahnoun
- Department of Nuclear Medicine, University Hospital RWTH Aachen University, Pauwelsstr. 31, 52074, Aachen, Germany
| | - Patrick Conen
- Department of Nuclear Medicine, University Hospital RWTH Aachen University, Pauwelsstr. 31, 52074, Aachen, Germany
| | - Felix M Mottaghy
- Department of Nuclear Medicine, University Hospital RWTH Aachen University, Pauwelsstr. 31, 52074, Aachen, Germany. .,Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, Cologne, Germany. .,Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, 6229 HX Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, Netherlands.
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Effraimidis G, Knigge U, Rossing M, Oturai P, Rasmussen ÅK, Feldt-Rasmussen U. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin Cancer Biol 2021; 79:141-162. [PMID: 33905872 DOI: 10.1016/j.semcancer.2021.04.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/03/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022]
Abstract
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.
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Affiliation(s)
- Grigoris Effraimidis
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Maria Rossing
- Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Åse Krogh Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulla Feldt-Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Denmark.
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Duclos V, Iep A, Gomez L, Goldfarb L, Besson FL. PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology. Int J Mol Sci 2021; 22:4159. [PMID: 33923839 PMCID: PMC8073681 DOI: 10.3390/ijms22084159] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 04/14/2021] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level.
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Affiliation(s)
- Valentin Duclos
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Alex Iep
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Léa Gomez
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
| | - Lucas Goldfarb
- Service Hospitalier Frédéric Joliot-CEA, 91401 Orsay, France;
| | - Florent L. Besson
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris Saclay, Assistance Publique-Hôpitaux de Paris, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France; (V.D.); (A.I.); (L.G.)
- Université Paris Saclay, CEA, CNRS, Inserm, BioMaps, 91401 Orsay, France
- School of Medicine, Université Paris Saclay, 94720 Le Kremlin-Bicêtre, France
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Garcia-Torralba E, Spada F, Lim KHJ, Jacobs T, Barriuso J, Mansoor W, McNamara MG, Hubner RA, Manoharan P, Fazio N, Valle JW, Lamarca A. Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis. Cancer Treat Rev 2021; 94:102168. [PMID: 33730627 DOI: 10.1016/j.ctrv.2021.102168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions. METHODS PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed . RESULTS A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS. CONCLUSIONS BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.
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Affiliation(s)
- Esmeralda Garcia-Torralba
- Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom; Department of Haematology and Medical Oncology, Hospital Morales Meseguer, Murcia, Spain
| | - Francesca Spada
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Kok Haw Jonathan Lim
- Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom; Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
| | - Timothy Jacobs
- Medical Library, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Jorge Barriuso
- Division of Cancer Sciences, University of Manchester, Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Was Mansoor
- Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester, Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Richard A Hubner
- Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Nicola Fazio
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Angela Lamarca
- Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
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Patel M, Tena I, Jha A, Taieb D, Pacak K. Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World. Front Endocrinol (Lausanne) 2021; 12:625312. [PMID: 33854479 PMCID: PMC8039528 DOI: 10.3389/fendo.2021.625312] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 03/04/2021] [Indexed: 12/16/2022] Open
Abstract
Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both "cold", particularly octreotide and lanreotide, and "hot" analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with 68Ga-DOTATATE and 177Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in succinate dehydrogenase subunit B gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of 68Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.
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Affiliation(s)
- Mayank Patel
- Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Isabel Tena
- Scientific Department, Medica Scientia Innovation Research (MedSIR), Barcelona, Spain
- Section of Medical Oncology, Consorcio Hospitalario Provincial of Castellon, Castellon, Spain
| | - Abhishek Jha
- Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - David Taieb
- Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France
| | - Karel Pacak
- Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
- *Correspondence: Karel Pacak,
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Impacto clínico del PET/TC Ga68-DOTATOC en tumores de origen neuroendocrino. Experiencia preliminar. ENDOCRINOL DIAB NUTR 2020; 67:636-642. [DOI: 10.1016/j.endinu.2019.12.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/12/2019] [Accepted: 12/23/2019] [Indexed: 12/28/2022]
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Draulans C, De Roover R, van der Heide UA, Kerkmeijer L, Smeenk RJ, Pos F, Vogel WV, Nagarajah J, Janssen M, Isebaert S, Maes F, Mai C, Oyen R, Joniau S, Kunze-Busch M, Goffin K, Haustermans K. Optimal 68Ga-PSMA and 18F-PSMA PET window levelling for gross tumour volume delineation in primary prostate cancer. Eur J Nucl Med Mol Imaging 2020; 48:1211-1218. [PMID: 33025093 DOI: 10.1007/s00259-020-05059-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 09/27/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS Nine 68Ga-PSMA-11 and nine 18F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTVmanual) and a majority-voted GTV (GTVmajority) were assessed with respect to a registered histopathological GTV (GTVhisto) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUVmax. The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTVhisto contour as training structure (GTVSOST-H) and second using the GTVmajority contour as training structure (GTVSOST-MA) to correct for any limited misregistration. The accuracy of both GTVSOST-H and GTVSOST-MA was calculated relative to GTVhisto in the 'leave-one-out' patient of each fold and compared with the accuracy of GTVmanual. RESULTS ROC curve analysis for 68Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTVSOST-H and GTVSOST-MA, respectively. For 18F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTVSOST-H and 44 SUV% (42-45 SUV%) for GTVSOST-MA was found. A significant pairwise difference was observed when comparing the accuracy of the GTVSOST-H contours with the median accuracy of the GTVmanual contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTVSOST-MA contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS Threshold-based contouring using GTVmajority-trained SOSTs achieves an accuracy comparable with manual contours in delineating GTVhisto. The median SOSTs of 41 SUV% for 68Ga-PSMA-11 PET and 44 SUV% for 18F-PSMA-1007 PET form a base for tracer-specific window levelling. TRIAL REGISTRATION Clinicaltrials.gov ; NCT03327675; 31-10-2017.
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Affiliation(s)
- Cédric Draulans
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.
- Department of Oncology, KU Leuven, Leuven, Belgium.
| | - Robin De Roover
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
- Department of Oncology, KU Leuven, Leuven, Belgium
| | - Uulke A van der Heide
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Linda Kerkmeijer
- Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
- Department of Radiation Oncology, University Medical Centre, Utrecht, The Netherlands
| | - Robert J Smeenk
- Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Floris Pos
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Wouter V Vogel
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - James Nagarajah
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Marcel Janssen
- Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Sofie Isebaert
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium
- Department of Oncology, KU Leuven, Leuven, Belgium
| | - Frederik Maes
- Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium
- Medical Imaging Research Centre, University Hospitals Leuven, Leuven, Belgium
| | - Cindy Mai
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Raymond Oyen
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Steven Joniau
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Martina Kunze-Busch
- Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Karolien Goffin
- Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Karin Haustermans
- Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.
- Department of Oncology, KU Leuven, Leuven, Belgium.
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Abstract
Neuroendocrine tumors are rare solid tumors with an estimated 12,000 people in the United States diagnosed each year. Neuroendocrine tumors can occur in any part of the body. There is a wide spectrum of disease, ranging from slow-growing and indolent tumors found incidentally to highly aggressive malignancies with a poor prognosis. Knowledge of neuroendocrine tumor pathology is essential in the diagnostic workup of these patients. This article focuses on the evaluation, detection, and staging of common neuroendocrine tumors with multiple imaging modalities; the information gained with a multimodality approach is often complementary and leads to image-guided treatment decision making.
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Affiliation(s)
- Samuel J Galgano
- Department of Radiology, Section of Abdominal Imaging, University of Alabama at Birmingham, 619 19th Street South, JT N325, Birmingham, AL 35249, USA; Department of Radiology, Section of Molecular Imaging & Therapeutics, University of Alabama at Birmingham, 619 19th Street South, JT N325, Birmingham, AL 35249, USA.
| | - Kedar Sharbidre
- Department of Radiology, Section of Abdominal Imaging, University of Alabama at Birmingham, 619 19th Street South, JT N325, Birmingham, AL 35249, USA
| | - Desiree E Morgan
- Department of Radiology, Section of Abdominal Imaging, University of Alabama at Birmingham, 619 19th Street South, JT N325, Birmingham, AL 35249, USA
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40
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Halfdanarson TR, Strosberg JR, Tang L, Bellizzi AM, Bergsland EK, O'Dorisio TM, Halperin DM, Fishbein L, Eads J, Hope TA, Singh S, Salem R, Metz DC, Naraev BG, Reidy-Lagunes DL, Howe JR, Pommier RF, Menda Y, Chan JA. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:863-881. [PMID: 32675783 DOI: 10.1097/mpa.0000000000001597] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
This article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.
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Affiliation(s)
| | | | - Laura Tang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Emily K Bergsland
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Thomas M O'Dorisio
- Department of Medicine, Division of Endocrinology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Lauren Fishbein
- Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Division of Biomedical Informatics and Personalized Medicine, University of Colorado School of Medicine, Aurora, CO
| | - Jennifer Eads
- Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Simron Singh
- Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago IL
| | - David C Metz
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | | | | | - James R Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Rodney F Pommier
- Department of Surgery, Oregon Health and Science University, Portland, OR
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
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41
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[ 18F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [ 68Ga]Ga-DOTATATE in neuroendocrine tumour patients. Eur J Nucl Med Mol Imaging 2020; 47:3033-3046. [PMID: 32617641 DOI: 10.1007/s00259-020-04918-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 06/07/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE The widespread use of gallium-68-labelled somatostatin analogue (SSA) PET, the current standard for somatostatin receptor (SSTR) imaging, is limited by practical and economic challenges that could be overcome by a fluorine-18-labelled alternative, such as the recently introduced [18F]AlF-NOTA-octreotide ([18F]AlF-OC). This prospective trial aimed to evaluate safety, dosimetry, biodistribution, pharmacokinetics and lesion targeting of [18F]AlF-OC and perform the first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour (NET) patients. METHODS Six healthy volunteers and six NET patients with a previous clinical [68Ga]Ga-DOTATATE PET were injected with an IV bolus of 4 MBq/kg [18F]AlF-OC. Healthy volunteers underwent serial whole-body PET scans from time of tracer injection up to 90 min post-injection, with an additional PET/CT at 150 and 300 min post-injection. In patients, a 45-min dynamic PET was acquired and three whole-body PET scans at 60, 90 and 180 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake (SUVmean) and tumour lesion uptake (SUVmax and tumour-to-background ratio (TBR)) were measured. A lesion-by-lesion analysis was performed and the detection ratio (DR), defined as the fraction of detected lesions was determined for each tracer. RESULTS [18F]AlF-OC administration was safe and well tolerated. The highest dose was received by the spleen (0.159 ± 0.062 mGy/MBq), followed by the urinary bladder wall (0.135 ± 0.046 mGy/mBq) and the kidneys (0.070 ± 0.018 mGy/MBq), in accordance with the expected SSTR-specific uptake in the spleen and renal excretion of the tracer. The effective dose was 22.4 ± 4.4 μSv/MBq. The physiologic uptake pattern of [18F]AlF-OC was comparable to [68Ga]Ga-DOTATATE. Mean tumour SUVmax was lower for [18F]AlF-OC (12.3 ± 6.5 at 2 h post-injection vs. 18.3 ± 9.5; p = 0.03). However, no significant differences were found in TBR (9.8 ± 6.7 at 2 h post-injection vs. 13.6 ± 11.8; p = 0.35). DR was high and comparable for both tracers (86.0% for [68Ga]Ga-DOTATATE vs. 90.1% for [18F]AlF-OC at 2 h post-injection; p = 0.68). CONCLUSION [18F]AlF-OC shows favourable kinetic and imaging characteristics in patients that warrant further head-to-head comparison to validate [18F]AlF-OC as a fluorine-18-labelled alternative for gallium-68-labelled SSA clinical PET. TRIAL REGISTRATION Clinicaltrials.gov : NCT03883776, EudraCT: 2018-002827-40.
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42
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de Geus-Oei LF, Deroose CM. Nuclear medicine in precision oncology: a foreword. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF RADIOPHARMACEUTICAL CHEMISTRY AND BIOLOGY 2020; 64:231-233. [PMID: 32343513 DOI: 10.23736/s1824-4785.20.03262-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.,Biomedical Photonic Imaging Group, University of Twente, Enschede, the Netherlands
| | - Christophe M Deroose
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium - .,Unit of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
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43
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The efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours: a systematic review and meta-analysis. J Cancer Res Clin Oncol 2020; 146:1533-1543. [PMID: 32281025 DOI: 10.1007/s00432-020-03181-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 03/11/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE To evaluate the efficacy of 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs), (PROSPERO ID CRD42019130755). METHODS All published clinical studies of NETs treated with 177Lu-DOTATATE were identified based on systematic searches in the PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov databases up to January 2019. Among these studies, only the reports evaluated with the "Response Evaluation Criteria in Solid Tumours (RECIST)" or "Southwest Oncology Group (SWOG)" criteria or both were included. We analysed the disease response rate (DRR) and disease control rate (DCR) of each group to evaluate the efficacy of 177Lu-DOTATATE. RESULTS Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs after177Lu-DOTATATE treatment, indicating that 177Lu-DOTATATE treatment has excellent efficacy with a control rate of approximately 78-79%. Moreover, adverse effects of 177Lu-DOTATATE were minimal, including fatigue, nausea, vomiting and hormonal disorders. CONCLUSIONS For patients with inoperable or metastatic NETs, 177Lu-DOTATATE is an effective treatment with minimal side effects.
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Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocr Rev 2020; 41:bnz004. [PMID: 31555796 PMCID: PMC7080342 DOI: 10.1210/endrev/bnz004] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 02/28/2020] [Indexed: 02/07/2023]
Abstract
Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options.
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Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
| | - Gregory Kaltsas
- 1st Department of Propaupedic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Wouter W de Herder
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
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45
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Signore A, Lauri C, Auletta S, Varani M, Onofrio L, Glaudemans AWJM, Panzuto F, Marchetti P. Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy. Cancers (Basel) 2020; 12:cancers12040781. [PMID: 32218303 PMCID: PMC7226069 DOI: 10.3390/cancers12040781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 12/12/2022] Open
Abstract
Molecular medicine has gained clinical relevance for the detection and staging of oncological diseases, to guide therapy decision making and for therapy follow-up due to the availability of new highly sensitive hybrid imaging camera systems and the development of new tailored radiopharmaceuticals that target specific molecules. The knowledge of the expression of different receptors on the primary tumor and on metastases is important for both therapeutic and prognostic purposes and several approaches are available aiming to achieve personalized medicine in different oncological diseases. In this review, we describe the use of specific radiopharmaceuticals to image and predict therapy response in breast cancer and neuroendocrine tumors since they represent a paradigmatic example of the importance of tumoral characterization of hormonal receptors in order to plan a tailored treatment. The most attractive radiopharmaceuticals for breast cancer are 16α-[18F]-fluoro-17β-estradiol for PET assessment of the estrogen expression, radiolabeled monoclonal antibody trastuzumab to image the human epidermal growth factor receptor 2, but also the imaging of androgen receptors with [18F]-fluorodihydrotestosterone.
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Affiliation(s)
- Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
- Correspondence:
| | - Chiara Lauri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Sveva Auletta
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Michela Varani
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
| | - Livia Onofrio
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
| | - Andor W. J. M. Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Francesco Panzuto
- Digestive Disease Unit, AOU Sant’Andrea and ENETS Center of Excellence, 00189 Rome, Italy;
| | - Paolo Marchetti
- Oncology Unit, Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, and IDI-IRCCS, 00189 Rome, Italy;
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Abstract
Neuroendocrine tumors of the gastrointestinal tract or pancreas are rare. Their presentation overlaps with other intra-abdominal neoplasms, but can have unique features. The workup involves recognition of unusual clinical features associated with the tumors, imaging, analysis of blood or urine concentrations, and biopsy. Functional imaging takes advantage of the neuroendocrine tumor-specific expression of somatostatin receptors. There are characteristic features supporting the diagnosis on contrast-enhanced cross-sectional imaging. The use of tumor markers for biochemical diagnosis requires an understanding of the confounding variables affecting these assays. There are unique and specific immunohistochemical staining and grading requirements for appropriate diagnosis of these tumors.
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Affiliation(s)
- Joseph S Dillon
- Division of Endocrinology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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47
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van Roekel C, Braat AJAT, Smits MLJ, Bruijnen RCG, de Keizer B, Lam MGEH. Radioembolization. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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48
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Pauwels E, Van Binnebeek S, Vandecaveye V, Baete K, Vanbilloen H, Koole M, Mottaghy FM, Haustermans K, Clement PM, Nackaerts K, Van Cutsem E, Verslype C, Deroose CM. Inflammation-Based Index and 68Ga-DOTATOC PET-Derived Uptake and Volumetric Parameters Predict Outcome in Neuroendocrine Tumor Patients Treated with 90Y-DOTATOC. J Nucl Med 2019; 61:1014-1020. [PMID: 31806775 DOI: 10.2967/jnumed.119.236935] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 11/21/2019] [Indexed: 12/11/2022] Open
Abstract
We performed post hoc analyses on the utility of pretherapeutic and early interim 68Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to 4 cycles of 90Y-DOTATOC at 1.85 GBq/m2/cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent 68Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUVmean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 cm3 (75th percentile) was associated with worse OS (HR, 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with progression-free survival were found. A composite score based on SUVmean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This method can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization.
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Affiliation(s)
- Elin Pauwels
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Sofie Van Binnebeek
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | | | - Kristof Baete
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Hubert Vanbilloen
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Michel Koole
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Felix M Mottaghy
- Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.,Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Karin Haustermans
- Radiation Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - Paul M Clement
- General Medical Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - Kristiaan Nackaerts
- Respiratory Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium; and
| | - Eric Van Cutsem
- Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - Chris Verslype
- Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
| | - Christophe M Deroose
- Nuclear Medicine, University Hospitals Leuven, and Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
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49
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The multidisciplinary team for gastroenteropancreatic neuroendocrine tumours: the radiologist's challenge. Radiol Oncol 2019; 53:373-387. [PMID: 31652122 PMCID: PMC6884929 DOI: 10.2478/raon-2019-0040] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 07/15/2019] [Indexed: 02/07/2023] Open
Abstract
Background Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a heterogeneous group of tumours. An effective diagnosis requires a multimodal approach that combines evaluation of clinical symptoms, hormonelevels, radiological and nuclear imaging, and histological confirmation. Imaging plays a critical role in NETs diagnosis, prognosis and management, so the radiologists are important members of the multidisciplinary team. During diagnostic work-up two critical issues are present: firstly the need to identify tumor presence and secondly to define the primary site and assess regional and distant metastases. Conclusions The most appropriate imaging technique depends on the type of neuroendocrine tumour and the availability of specialized imaging techniques and expertise. There is no general consensus on the most efficient imaging pathway, reflecting the challenge in reliably detection of these tumours.
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50
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Zheng Z, Chen C, Jiang L, Zhou X, Dai X, Song Y, Li Y. Incidence and risk factors of gastrointestinal neuroendocrine neoplasm metastasis in liver, lung, bone, and brain: A population-based study. Cancer Med 2019; 8:7288-7298. [PMID: 31609098 PMCID: PMC6885880 DOI: 10.1002/cam4.2567] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/03/2019] [Accepted: 09/09/2019] [Indexed: 12/24/2022] Open
Abstract
Background Neuroendocrine neoplasm is a rare solid tumor. Metastatic pattern of the gastrointestinal neuroendocrine neoplasm (GI‐NEN) has not been fully explored. Methods Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (SEER‐9 registry) from 1973 to 2015. Incidence was estimated by Joinpoint regression analyses. Data with additional treatment fields of GI‐NEN were extracted from the SEER‐18 registry from 1 January 2010 to 31 December 2015. A total of 14 685 GI‐NEN patients were included in this study. Statistical analyses were performed with SPSS 25.0, the Intercooled Stata SE 15.0, and GraphPad Prism 7. Results Incidence of GI‐NENs increased from 0.51 per 100 000 patients in 1973 to 6.20 per 100 000 patients in 2015. Of them, 2003 patients were stage IV GI‐NEN at the time of diagnosis, including 1459 (72.84%) patients with liver metastasis, 144 (7.19%) lung metastasis, 115 (5.74%) bone metastasis, and 27 (1.35%) brain metastasis. Esophageal NEN had the highest risk of metastasis (52.68%). The median survival for patients with liver, lung, bone, and brain metastasis was 38, 6, 9, and 2 months, respectively. The presence of lung or liver metastasis indicated higher risk of concurrent existence of bone and brain metastasis than those without. Conclusion Bone and brain metastasis should be screened in the GI‐NEN patients if they had lung or liver metastasis. Findings of the current study could help clinicians to identify distant metastasis of GI‐NENs as early as possible, and by which, to improve survival rate of GI‐NENs.
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Affiliation(s)
- Zhibo Zheng
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Chuyan Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Lingjuan Jiang
- Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xingtong Zhou
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoyan Dai
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yimin Song
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yongning Li
- Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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