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Karim H, Winkelmann M, Grawe F, Völter F, Auernhammer C, Rübenthaler J, Ricke J, Ingenerf M, Schmid-Tannwald C. Quantitative SSTR-PET/CT: a potential tool for predicting everolimus response in neuroendoctine tumour patients. Radiol Oncol 2024; 58:348-356. [PMID: 38861687 PMCID: PMC11406901 DOI: 10.2478/raon-2024-0032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/10/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND This study aimed to assess 68Ga-DOTA-TATE (-TOC) PET/CT quantitative parameters in monitoring and predicting everolimus response in neuroendocrine tumor (NET) patients with hepatic metastases (NELM). PATIENTS AND METHODS This retrospective analysis included 29 patients with 62 target lesions undergoing everolimus treatment and pre-therapy, and follow-up 68Ga-DOTA-TATE (-TOC) PET/CT scans. Response evaluation utilized progression-free survival (PFS) categorized as responders (R; PFS > 6 months) and non-responders (NR; PFS ≤ 6 months). Lesion size and density, along with maximum and median standardize uptake value (SUV) in target lesions, liver, and spleen were assessed. Tumor-to-spleen (T/S) and tumor-to-liver (T/L) ratios were calculated, including the tumor-to-spleen (T/S) ratio and tumor-to-liver (T/L) ratio (using SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean). RESULTS PET/CT scans were acquired 19 days (interquartile range [IQR] 69 days) pre-treatment and 127 days (IQR 74 days) post-starting everolimus. The overall median PFS was 264 days (95% CI: 134-394 days). R exhibited significant decreases in Tmax/Lmax and Tmean/Lmax ratios compared to NR (p = 0.01). In univariate Cox regression, Tmean/Lmax ratio was the sole prognostic parameter associated with PFS (HR 0.5, 95% CI 0.28-0.92, p = 0.03). Percentage changes in T/L and T/S ratios were significant predictors of PFS, with the highest area under curve (AUC) for the percentage change of Tmean/Lmax (AUC = 0.73). An optimal threshold of < 2.5% identified patients with longer PFS (p = 0.003). No other imaging or clinical parameters were predictive of PFS. CONCLUSIONS This study highlights the potential of quantitative SSTR-PET/CT in predicting and monitoring everolimus response in NET patients. Liver metastasis-to-liver parenchyma ratios outperformed size-based criteria, and Tmean/Lmax ratio may serve as a prognostic marker for PFS, warranting larger cohort investigation.
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Affiliation(s)
- Homeira Karim
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Michael Winkelmann
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Freba Grawe
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Friederike Völter
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Christoph Auernhammer
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
- Department of Internal Medicine 4, University Hospital, LMU Munich, Munich, Germany
| | - Johannes Rübenthaler
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
| | - Maria Ingenerf
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Christine Schmid-Tannwald
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
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Ingenerf M, Karim H, Auernhammer C, Zacherl M, Wenter V, Winkelmann M, Ricke J, Berger F, Schmid-Tannwald C. Quantitative SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM. Radiol Oncol 2023; 57:436-445. [PMID: 38038419 PMCID: PMC10690751 DOI: 10.2478/raon-2023-0055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/25/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND This study aimed to evaluate the predictive and monitoring role of somatostatin receptor (SSTR) positron emission tomography-computed tomography (PET/CT) and clinical parameters in patients with neuroendocrine liver metastases (NELM) from pancreatic neuroendocrine tumors (pNET) receiving capecitabine and temozolomide (CAPTEM). PATIENTS AND METHODS This retrospective study included twenty-two patients with pNET and NELM receiving CAPTEM who underwent pre- and post-therapeutic 68Ga-DOTATATE/-TOC PET/CT. Imaging (including standardized uptake value [SUV] of target lesions [NELM and pNET], normal spleen and liver) and clinical (Chromogranin A [CgA], Ki-67) parameters were assessed. Treatment outcome was evaluated as response according to RECIST 1.1, progression free survival (PFS) and overall survival (OS). RESULTS The median PFS (mPFS) was 7 months. Responders had a significantly longer mPFS compared to non-responders (10 vs. 4 months p = 0.022). Median OS (mOS) was 33 months (mOS: responders = 80 months, non-responders = 24 months p = 0.182). Baseline imaging showed higher SUV in responders, including absolute SUV, tumor-to-spleen (T/S), and tumor-to-liver (T/L) ratios (p < 0.02). All SUV parameters changed only in the responders during follow-up. Univariable Cox regression analysis identified baseline Tmax/Smean ratio and percentage change in size of pNETs as significant factors associated with PFS. A baseline Tmax/Smean ratio < 1.5 was associated with a shorter mPFS (10 vs. 4 months, (p < 0.05)). Prognostic factors for OS included age, percentage change in CgA and in T/S ratios in univariable Cox regression. CONCLUSIONS SSTR-PET/CT can be useful for predicting response and survival outcomes in pNET patients receiving CAPTEM: Higher baseline SUV values, particularly Tmax/Smean ratios of liver metastases were associated with better response and prolonged PFS.
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Affiliation(s)
- Maria Ingenerf
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Homeira Karim
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Christoph Auernhammer
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
- Department of Internal Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Matthias Zacherl
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Vera Wenter
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Michael Winkelmann
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
| | - Frank Berger
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Christine Schmid-Tannwald
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
- ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany
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Weber M, Telli T, Kersting D, Seifert R. Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors. Cancers (Basel) 2023; 15:3581. [PMID: 37509242 PMCID: PMC10377105 DOI: 10.3390/cancers15143581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/30/2023] Open
Abstract
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
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Affiliation(s)
- Manuel Weber
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Tugce Telli
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - David Kersting
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Robert Seifert
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
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Xie J, Zhang Y, He M, Liu X, Xie P, Pang Y. Survival comparison between endoscopic and surgical resection for non-ampullary duodenal neuroendocrine tumor (1-2 cm). Sci Rep 2022; 12:15339. [PMID: 36097200 PMCID: PMC9468163 DOI: 10.1038/s41598-022-19725-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 09/02/2022] [Indexed: 11/09/2022] Open
Abstract
The treatment plan for non-ampullary duodenal neuroendocrine tumors (d-NETs) with diameters 1-2 cm remains controversial. We therefore aimed to compare the prognostic effects of endoscopic treatment and surgical resection on non-ampullary d-NETs with 1-2 cm diameters. A total of 373 eligible patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to match patients 1:1 according to clinicopathological characteristics. Disease-specific survival (DSS) and overall survival (OS) were calculated. Before PSM, there was no significant difference in DSS or OS (all P > 0.05), but the T stage, N stage, and TNM stage were significantly different between the two surgical methods (all P < 0.05). After 1:1 PSM, the differences in clinicopathological characteristics were significantly reduced (all P > 0.05). Survival analysis showed that tumor grade was correlated with DSS and that age was correlated with OS (all P < 0.05); however, the surgical method and other clinicopathological characteristics were not correlated with prognosis (all P > 0.05). Subgroup survival analysis of patients with T2N0M0 disease and tumors invading the lamina propria or submucosa showed that the 5-year DSS and OS rates were not significantly different according to the surgical approach (all P > 0.05). The surgical approach has no significant effect on the prognosis of patients with non-ampullary d-NETs with 1-2 cm diameters, especially those with T2N0M0 disease. This suggests that endoscopic treatment may be a preferred option for these patients.
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Affiliation(s)
- Jiebin Xie
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Yuan Zhang
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Ming He
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Xu Liu
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Pin Xie
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China
| | - Yueshan Pang
- Department of Geriatrics, The Second Clinical Medical College of North Sichuan Medical College, Nanchong Central Hospital, Nanchong, 637100, Sichuan, People's Republic of China.
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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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Pepe G, Matassa G, Piccoli F, Chiti A. Advances in Diagnostic Imaging. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:75-98. [DOI: 10.1007/978-3-030-72830-4_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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Bauckneht M, Albano D, Annunziata S, Santo G, Guglielmo P, Frantellizzi V, Branca A, Ferrari C, Vento A, Mirabile A, Nappi AG, Evangelista L, Alongi P, Laudicella R. Somatostatin Receptor PET/CT Imaging for the Detection and Staging of Pancreatic NET: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2020; 10:598. [PMID: 32824388 PMCID: PMC7459584 DOI: 10.3390/diagnostics10080598] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022] Open
Abstract
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71-87%) and 95% (95%CI: 75-100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65-90%) and 92% (95%CI: 80-97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs.
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Affiliation(s)
- Matteo Bauckneht
- Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;
| | - Domenico Albano
- Department of Nuclear Medicine, University of Brescia and Spedali Civili Brescia, 25123 Brescia, Italy;
| | - Salvatore Annunziata
- Nuclear Medicine Unit, IRCSS Regina Elena National Cancer Institute, 00168 Rome, Italy;
| | - Giulia Santo
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | | | - Viviana Frantellizzi
- Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Alessia Branca
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Cristina Ferrari
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Antonio Vento
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
| | - Alessia Mirabile
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
| | - Anna Giulia Nappi
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy
| | - Pierpaolo Alongi
- Unit of Nuclear Medicine, Fondazione Istituto G.Giglio, 90015 Cefalù, Italy;
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
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Heinemann F, Guhlke S, Muckle M, Willinek W, Biersack HJ, Ahmadzadehfar H, Sabet A, Ezziddin S. Osseous metastases of gastro- entero - pancreatic neuroendocrine tumours. Nuklearmedizin 2017; 51:95-100. [DOI: 10.3413/nukmed-0428-11-08] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2011] [Accepted: 01/10/2012] [Indexed: 12/30/2022]
Abstract
SummaryAim: Peptide receptor radionuclide therapy with 177Lu-octreotate is an effective treatment option for metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET) and allows intratherapeutic imaging through a 177Lu-octreotate scan (LuS). The diagnostic value of this treatment scan is not yet established. This study aims to compare the sensitivity of LuS and bone scintigraphy (BS) regarding bone metastases and investigate potential implications of functional imaging results. Patients, methods: We retrospectively analyzed 29 consecutive GEP NET patients with bone metastases and baseline BS treated with 177Lu-octreotate. A semi-quantitative scoring system was used for the comparative evaluation. Treatment outcome (time-to-progression of bone metastases) was correlated with the intra-individual imaging discrepancy (Kaplan- Meyer curves, log-rank test, p < 0.05). Results: In 19 of 29 patients (65.5%) LuS was superior (LuS > BS), whereas in 10 patients (34.5%) both modalities were comparable. BS showed no additional (LuS-negative) metastatic bone lesions in our cohort. None of the investigated baseline characteristics was associated with Imaging discrepancy. On the other hand, functional imaging discrepancy had no impact on treatment response (p = 0.43) or time-to-progression (p = 0.92). Conclusions: Intra-therapeutic 177Lu-octreotate imaging is superior over bone scintigraphy for detection of bone metastases in GEP NET. BS may help to distinguish osseous from non-osseous localization. The presence of an osteoblastic correlate in BS seems to have no impact on therapeutic outcome
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Manoharan J, Albers MB, Bartsch DK. The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer 2017; 24:T209-T225. [PMID: 28790162 DOI: 10.1530/erc-17-0231] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Accepted: 08/08/2017] [Indexed: 12/13/2022]
Abstract
Prospective randomized data are lacking, but current clinical expert guidelines recommend annual screening examinations, including laboratory assessments and various imaging modalities (e.g. CT, MRI, scintigraphy and EUS) for patients with multiple endocrine neoplasia type 1 (MEN1). Routine screening is proposed to detect and localize neuroendocrine manifestations as early as possible. The goal is timely intervention to improve quality of life and to increase life expectancy by preventing the development of life-threatening hormonal syndromes and/or metastatic disease. In recent years, some studies compared different and new imaging methods regarding their sensitivity and utility in MEN1 patients. This present article reviews the proposed diagnostic tools for MEN1 screening as well as potential future perspectives.
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Affiliation(s)
- Jerena Manoharan
- Department of VisceralThoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Max B Albers
- Department of VisceralThoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Detlef K Bartsch
- Department of VisceralThoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
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10
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Graham MM, Gu X, Ginader T, Breheny P, Sunderland JJ. 68Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis. J Nucl Med 2017; 58:1452-1458. [PMID: 28280220 PMCID: PMC6944175 DOI: 10.2967/jnumed.117.191197] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 02/17/2017] [Indexed: 12/13/2022] Open
Abstract
68Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of 68Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. Methods: The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with 111In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. Results: The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with 111In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for 111In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Conclusion:68Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than 111In-octreotide. Although 68Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.
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Affiliation(s)
- Michael M Graham
- Division of Nuclear Medicine, Department of Radiology, University of Iowa, Iowa City, Iowa
| | - Xiaomei Gu
- Hardin Library for the Health Sciences, University of Iowa, Iowa City, Iowa; and
| | - Timothy Ginader
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
| | - Patrick Breheny
- Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
| | - John J Sunderland
- Division of Nuclear Medicine, Department of Radiology, University of Iowa, Iowa City, Iowa
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11
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Riechelmann RP, Weschenfelder RF, Costa FP, Andrade AC, Osvaldt AB, Quidute ARP, Dos Santos A, Hoff AAO, Gumz B, Buchpiguel C, Vilhena Pereira BS, Lourenço Junior DM, da Rocha Filho DR, Fonseca EA, Riello Mello EL, Makdissi FF, Waechter FL, Carnevale FC, Coura-Filho GB, de Paulo GA, Girotto GC, Neto JEB, Glasberg J, Casali-da-Rocha JC, Rego JFM, de Meirelles LR, Hajjar L, Menezes M, Bronstein MD, Sapienza MT, Fragoso MCBV, Pereira MAA, Barros M, Forones NM, do Amaral PCG, de Medeiros RSS, Araujo RLC, Bezerra ROF, Peixoto RD, Aguiar S, Ribeiro U, Pfiffer T, Hoff PM, Coutinho AK. Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group. Ecancermedicalscience 2017; 11:716. [PMID: 28194228 PMCID: PMC5295846 DOI: 10.3332/ecancer.2017.716] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
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Affiliation(s)
- Rachel P Riechelmann
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | | | | | | | - Alessandro Bersch Osvaldt
- Hospital Moinhos de Vento de Porto Alegre, Porto Alegre 90035-000, Brasil; Departamento de Cirurgia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90040-060, Brasil; Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, Brasil
| | - Ana Rosa P Quidute
- Departamento de Fisiologia e Farmacologia da Faculdade de Medicina da Universidade Federal do Ceará, Fortaleza 60020-180, Brasil; Hospital Universitário Walter Cantidio, Ceará 60430-370, Brasil
| | | | - Ana Amélia O Hoff
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - Brenda Gumz
- Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - Carlos Buchpiguel
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil
| | | | - Delmar Muniz Lourenço Junior
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil
| | | | - Eduardo Antunes Fonseca
- Hospital Sírio-Libanês, São Paulo 01308-050, Brasil; Department of Surgery, AC Camargo Cancer Centre, São Paulo 01509-010, Brasil
| | | | - Fabio Ferrari Makdissi
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil
| | - Fabio Luiz Waechter
- Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050-170, Brasil
| | - Francisco Cesar Carnevale
- Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - George B Coura-Filho
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil
| | - Gustavo Andrade de Paulo
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Hospital Albert Einstein, São Paulo 05652-900, Brasil
| | - Gustavo Colagiovanni Girotto
- Hospital de Base da Faculdade de Medicina de São José do Rio Preto, São Paulo 15090-000, Brasil; Santa Casa de São José do Rio Preto, São José do Rio Preto 15025-500, Brasil
| | - João Evangelista Bezerra Neto
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - João Glasberg
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil
| | | | | | | | - Ludhmila Hajjar
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Instituto do Coração, Universidade de São Paulo, São Paulo 05403-900, Brasil
| | - Marcos Menezes
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - Marcello D Bronstein
- Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil
| | - Marcelo Tatit Sapienza
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil
| | - Maria Candida Barisson Villares Fragoso
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Disciplina de Endocrinologia e Metabologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil
| | | | - Milton Barros
- Medical Oncology, AC Camargo Cancer Centre, São Paulo 01509-010, Brasil
| | - Nora Manoukian Forones
- Disciplina de Gastroenterologia, Universidade Federal de São Paulo, São Paulo 04021-001, Brasil
| | | | | | - Raphael L C Araujo
- Departamento de Cirurgia do Aparelho Digestivo Alto e Hepato-Bilio-Pancreática, Hospital de Câncer de Barretos, São Paulo 14784-400, Brasil
| | | | - Renata D'Alpino Peixoto
- Hospital São José, São Paulo 01323-001, Brasil; Universidade Nove de Julho, São Paulo 02111-030, Brasil
| | - Samuel Aguiar
- Medical Oncology, AC Camargo Cancer Centre, São Paulo 01509-010, Brasil
| | - Ulysses Ribeiro
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil
| | - Tulio Pfiffer
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
| | - Paulo M Hoff
- Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo 01246-000, Brasil; Departamento de Radiologia e Oncologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil; Hospital Sírio-Libanês, São Paulo 01308-050, Brasil
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12
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Dromain C, Déandréis D, Scoazec JY, Goere D, Ducreux M, Baudin E, Tselikas L. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging 2016; 97:1241-1257. [PMID: 27876341 DOI: 10.1016/j.diii.2016.07.012] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 07/18/2016] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.
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Affiliation(s)
- C Dromain
- Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland.
| | - D Déandréis
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - J-Y Scoazec
- Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - D Goere
- Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - M Ducreux
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - E Baudin
- Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - L Tselikas
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
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13
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Virgolini I, Gabriel M, Kroiss A, von Guggenberg E, Prommegger R, Warwitz B, Nilica B, Roig LG, Rodrigues M, Uprimny C. Current knowledge on the sensitivity of the (68)Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2016; 43:2072-83. [PMID: 27174220 PMCID: PMC5007271 DOI: 10.1007/s00259-016-3395-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 04/11/2016] [Indexed: 02/08/2023]
Abstract
Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three 68Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these 68Ga-sstr-binding peptides in the imaging setting. On 68Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with 68Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.
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Affiliation(s)
- Irene Virgolini
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
| | - Michael Gabriel
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Alexander Kroiss
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Elisabeth von Guggenberg
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Rupert Prommegger
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Boris Warwitz
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Bernhard Nilica
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Llanos Geraldo Roig
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Margarida Rodrigues
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Christian Uprimny
- Department of Nuclear Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
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14
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Yu R. Animal models of spontaneous pancreatic neuroendocrine tumors. Mol Cell Endocrinol 2016; 421:60-7. [PMID: 26261055 DOI: 10.1016/j.mce.2015.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 07/10/2015] [Accepted: 08/04/2015] [Indexed: 01/20/2023]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are usually low-grade neoplasms derived from the endocrine pancreas. PNETs can be functioning and cause well-described hormonal hypersecretion syndromes or non-functioning and cause only tumor mass effect. PNETs appear to be more common recently likely due to incidental detection by imaging. Although the diagnosis and management of PNETs have been evolving rapidly, much remains to be studied in the areas of molecular pathogenesis, molecular markers of tumor behavior, early detection, and targeted drug therapy. Unique challenges facing PNETs studies are long disease course, the deep location of pancreas and difficult access to pancreatic tissue, and the variety of tumors, which make animal models valuable tools for PNETs studies. Existing animal models of PNETs have provided insights into the pathogenesis and natural history of human PNETs. Future studies on animal models of PNETs should address early tumor detection, molecular markers of tumor behavior, and novel targeted therapies.
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Affiliation(s)
- Run Yu
- Division of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
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15
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Maxwell JE, O'Dorisio TM, Howe JR. Biochemical Diagnosis and Preoperative Imaging of Gastroenteropancreatic Neuroendocrine Tumors. Surg Oncol Clin N Am 2015; 25:171-94. [PMID: 26610781 DOI: 10.1016/j.soc.2015.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Neuroendocrine tumors are a group of neoplasms that can arise in a variety of locations throughout the body and often metastasize early. A patient's only chance for cure is surgical removal of the primary tumor and all associated metastases, although even when surgical cure is unlikely, patients can benefit from surgical debulking. A thorough preoperative workup will often require multiple clinical tests and imaging studies to locate the primary tumor, delineate the extent of the disease, and assess tumor functionality. This review discusses the biomarkers important for the diagnosis of these tumors and the imaging modalities needed.
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Affiliation(s)
- Jessica E Maxwell
- Department of General Surgery, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Thomas M O'Dorisio
- Department of Internal Medicine, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - James R Howe
- Department of General Surgery, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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16
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Johnbeck CB, Knigge U, Kjær A. PET tracers for somatostatin receptor imaging of neuroendocrine tumors: current status and review of the literature. Future Oncol 2015; 10:2259-77. [PMID: 25471038 DOI: 10.2217/fon.14.139] [Citation(s) in RCA: 121] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide, (68)Ga-DOTA-Tyr3-octreotate and (68)Ga-DOTA-l-Nal3-octreotide - shows little difference and expertise on the specific tracer used, and knowledge regarding physiological uptake might be more important than in vitro-proven differences in affinity. Using isotopes such as (18)F or (64)Cu might improve these PET tracers further.
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Affiliation(s)
- Camilla Bardram Johnbeck
- Department of Clinical Physiology, Nuclear Medicine & PET & Cluster for Molecular Imaging, Rigshospitalet & University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
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17
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Lococo F, Perotti G, Cardillo G, De Waure C, Filice A, Graziano P, Rossi G, Sgarbi G, Stefanelli A, Giordano A, Granone P, Rindi G, Versari A, Rufini V. Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid. Clin Nucl Med 2015; 40:e183-9. [PMID: 25608152 DOI: 10.1097/rlu.0000000000000641] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. METHODS Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUV max, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga-DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio). Histology was used as reference standard. RESULTS Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUV max ratio was the most accurate semiquantitative index in identifying TC. CONCLUSIONS Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUV max ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.
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Affiliation(s)
- Filippo Lococo
- From the *Unit of Thoracic Surgery, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia; †Institute of Nuclear Medicine, Università Cattolica del Sacro Cuore; ‡Unit of Thoracic Surgery, Azienda Ospedaliera San Camillo Forlanini; and §Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome; ∥Department of Nuclear Medicine, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia; ¶Unit of Pathology, Azienda Ospedaliera San Camillo Forlanini, Rome; #Unit of Pathology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia; **Department of Thoracic Surgery, and ††Institute of Pathology, Università Cattolica del Sacro Cuore, Rome, Italy
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Abstract
Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer (111)In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also (11)C-5-HTP, (18)F-DOPA and (123)I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established.
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Affiliation(s)
- Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen, Denmark,European NET Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,Correspondence: Andreas Kjaer, Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
| | - Ulrich Knigge
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen, Denmark,Departments of Surgery Cand Endocrinology PE, Copenhagen, Denmark,European NET Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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19
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Pfeifer A, Knigge U, Binderup T, Mortensen J, Oturai P, Loft A, Berthelsen AK, Langer SW, Rasmussen P, Elema D, von Benzon E, Højgaard L, Kjaer A. 64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients. J Nucl Med 2015; 56:847-54. [PMID: 25952736 DOI: 10.2967/jnumed.115.156539] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 04/10/2015] [Indexed: 12/12/2022] Open
Abstract
UNLABELLED Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of (64)Cu-DOTATATE and (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ((111)In-DTPA-OC) as a basis for implementing (64)Cu-DOTATATE as a routine. METHODS We prospectively enrolled 112 patients with pathologically confirmed NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with (111)In-DTPA-OC within 60 d. PET scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of (64)Cu-DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used to compare the diagnostic performance. RESULTS Eighty-seven patients were congruently PET- and SPECT-positive. No SPECT-positive cases were PET-negative, whereas 10 false-negative SPECT cases were identified using PET. The diagnostic sensitivity and accuracy of (64)Cu-DOTATATE (97% for both) were significantly better than those of (111)In-DTPA-OC (87% and 88%, respectively, P = 0.017). In 84 patients (75%), (64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC and always at least as many. In total, twice as many lesions were detected with (64)Cu-DOTATATE than with (111)In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by (64)Cu-DOTATATE in organs not identified as disease-involved by (111)In-DTPA-OC. CONCLUSION With these results, we demonstrate that (64)Cu-DOTATATE is far superior to (111)In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of (64)Cu-DOTATATE as a replacement for (111)In-DTPA-OC.
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Affiliation(s)
- Andreas Pfeifer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark Department of Nuclear Medicine, Helios-Klinikum Berlin-Buch, Berlin, Germany ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Ulrich Knigge
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark Departments of Surgical Gastroenterology C and Medical Endocrinology, Rigshospitalet, Copenhagen, Denmark
| | - Tina Binderup
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Jann Mortensen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Annika Loft
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Anne Kiil Berthelsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Seppo W Langer
- ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark Department of Oncology, Rigshospitalet, Copenhagen, Denmark; and
| | | | | | - Eric von Benzon
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Liselotte Højgaard
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark ENETS Center of Excellence for Neuroendocrine Tumors, Copenhagen, Denmark
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Sharma P, Arora S, Dhull VS, Naswa N, Kumar R, Ammini AC, Bal C. Evaluation of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors. ABDOMINAL IMAGING 2015; 40:299-309. [PMID: 25134801 DOI: 10.1007/s00261-014-0219-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
PURPOSE To evaluate the diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors (NETs). METHODS Data of 141 (mean age 46.2 ± 15.2 years) patients who underwent 178 (68)Ga-DOTANOC PET/CT studies for diagnosis/staging (n = 88) and restaging (n = 90) of pancreatic NET were retrospectively analyzed. PET/CT results were compared to conventional imaging (CIM) when available (n = 86). Histopathology and/or clinical/imaging follow-up (minimum 6 months) were used as reference standard. RESULTS The overall sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT were 85.7%, 79.1%, and 84.8%. The corresponding values were 73%, 50%, and 70.4% for diagnosis/staging groups and 98.6%, 100%, and 98.8% for restaging groups. The accuracy was significantly higher for restaging as compared to diagnosis/staging (P < 0.0001) and in non-insulinoma tumors than insulinomas (P < 0.0001). The SUVmax of primary tumors was significantly higher than metastatic lesions overall (P = 0.001), as well as in diagnosis/staging (P = 0.041) and restaging (P = 0.0003) subgroups. When available, CIM was less specific than (68)Ga-DOTANOC PET/CT (P < 0.001) and showed fewer lesions. CONCLUSIONS (68)Ga-DOTANOC PET/CT is useful for diagnosis/staging and restaging of patients with pancreatic NET. It demonstrates more lesions compared to CIM and is more specific.
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Affiliation(s)
- Punit Sharma
- Department of Nuclear Medicine and PET/CT, Eastern Diagnostics India Ltd., Kolkata, India,
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Abstract
The early and accurate characterization of pancreatic masses remains a challenge in diagnostic radiology, while the continuously evolving diagnostic possibilities give rise to an ever-increasing number of incidentally found pancreatic masses. This article discusses the relevance and role of ultrasound, endoscopic ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) in the diagnosis of pancreatic lesions. Specific protocols such as MR cholangiopancreatography and multiphase CT allow for a close characterization. While CT and MRI deliver information to further evaluate pancreatic disease, PET/CT has shown potential for staging purposes and in the clinical follow-up of pancreatic cancer patients. Common differential diagnoses regarding pancreatic cancer are discussed, and typical imaging features of anatomical variations, cystic lesions and pancreatitis are illustrated, together with clinical signs of pancreatic disease. The use of cross-sectional imaging in correlation with clinical features allows for an accurate and early detection of pancreatic masses and assists in differentiating benign from malignant disease.
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Affiliation(s)
- Daniel Putzer
- Department of Radiology, Innsbruck Medical University, Innsbruck, Austria
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Shamiyeh A, Gabriel M. Laparoscopic resection of gastrointestinal neuroendocrine tumors with special contribution of radionuclide imaging. World J Gastroenterol 2014; 20:15608-15. [PMID: 25400444 PMCID: PMC4229525 DOI: 10.3748/wjg.v20.i42.15608] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/22/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023] Open
Abstract
The surgical treatment of neuroendocrine tumors (NETs) draws on experience and guidelines more than on prospective randomized trials. The incidence of NET is increasing in all parts of the gastrointestinal tract. A variety of classifications introduced over the last decade may have led to difficulties in judging clinical relevance and determining the right surgical strategy. The North American Neuroendocrine Tumor Society and the European Neuroendocrine Tumor Society have developed usable guidelines from the available literature. For more than 20 years laparoscopy has developed as the gold standard for various surgical indications. Nevertheless, few trials have compared open and laparoscopic surgery with regard to NET. This review summarizes the recent literature on surgery for NET and incorporates the evidence on laparoscopy for cancer which might be also applied for NET.
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Lv J, Pan Y, Li X, Cheng D, Liu S, Shi H, Zhang Y. The imaging of insulinomas using a radionuclide-labelled molecule of the GLP-1 analogue liraglutide: a new application of liraglutide. PLoS One 2014; 9:e96833. [PMID: 24805918 PMCID: PMC4013070 DOI: 10.1371/journal.pone.0096833] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 04/13/2014] [Indexed: 01/17/2023] Open
Abstract
Objective This study explores a new, non-invasive imaging method for the specific diagnosis of insulinoma by providing an initial investigation of the use of 125I-labelled molecules of the glucagon-like peptide-1 (GLP-1) analogue liraglutide for in vivo and in vitro small-animal SPECT/CT (single-photon emission computed tomography/computed tomography) imaging of insulinomas. Methods Liraglutide was labelled with 125I by the Iodogen method. The labelled 125I-liraglutide compound and insulinoma cells from the INS-1 cell line were then used for in vitro saturation and competitive binding experiments. In addition, in a nude mouse model, the use of 125I-liraglutide for the in vivo small-animal SPECT/CT imaging of insulinomas and the resulting distribution of radioactivity across various organs were examined. Results The labelling of liraglutide with 125I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (Kd) was 128.8±30.4 nmol/L(N = 3), and the half-inhibition concentration (IC50) was 542.4±187.5 nmol/L(N = 3). Small-animal SPECT/CT imaging with 125I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125I-liraglutide treatment, the target/non-target (T/NT) ratio for tumour and muscle tissue was 4.83±1.30(N = 3). Our study suggested that 125I-liraglutide was predominantly metabolised and cleared by the liver and kidneys. Conclusion The radionuclide 125I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.
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Affiliation(s)
- Jing Lv
- Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Pan
- Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Li
- Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China
| | - Dengfeng Cheng
- Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China
| | - Shuai Liu
- Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China
| | - Yifan Zhang
- Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol 2014; 55:389-98. [PMID: 23928010 DOI: 10.1177/0284185113496679] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. PURPOSE To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. MATERIAL AND METHODS A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. RESULTS Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. CONCLUSION The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.
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Affiliation(s)
- Jigang Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Ying Kan
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Benjamin H Ge
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Leilei Yuan
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Chunlin Li
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Wenrui Zhao
- Department of Nuclear Medicine, Navy General Hospital, Hai Dian District, PR China
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Detection of neuroendocrine tumours in the small intestines using contrast-enhanced multiphase Ga-68 DOTATOC PET/CT: the potential role of arterial hyperperfusion. Radiol Oncol 2014; 48:120-6. [PMID: 24991201 PMCID: PMC4078030 DOI: 10.2478/raon-2014-0012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 10/24/2013] [Indexed: 01/28/2023] Open
Abstract
Background Interpretation of small intestinal neuroendocrine tumours (NETs) by Ga-68 DOTATOC PET/CT can be difficult. The potential benefit of arterial hyperperfusion for the detection of NETs was evaluated. Methods Between 2006 and 2009, 320 consecutive Ga-68 DOTATOC PET/CT examinations, performed for NETs, revealed 40 lesions suggesting intestinal NETs in 25 patients. Two groups of lesions were distinguished: epigastric lesions evaluable in the arterial and venous CT scan (Group 1) and hypogastrial lesions evaluable in the venous CT scan only (Group 2). Lesions were jointly rated by two radiologists and a nuclear medicine physician. Maximum standard uptake values (SUVmax) of lesions and background were assessed. The reference standard was histology (available for 28 lesions) or follow-up (for a mean of 22.9 months). Results PET detected all suspicious lesions but was false positive in 3 lesions. In Group 1 the arterial scan performed significantly better than the venous scan (p = 0.008). Diagnostic performance was better in Group 1 than in Group 2 (p < 0.001). SUVmax of true positive lesions were significantly higher than background SUVmax (p < 0.001) and SUVmax of false positive lesions (p = 0.005). Conclusions The arterial phase of multiphase Ga-68 DOTATOC PET/CT might improve the localization of intestinal NETs and, thereby, improve the overall diagnostic accuracy of this modality in the assessment of intestinal NETs by adding information about lesion perfusion not available when only venous CT is performed.
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van Essen M, Sundin A, Krenning EP, Kwekkeboom DJ. Neuroendocrine tumours: the role of imaging for diagnosis and therapy. Nat Rev Endocrinol 2014; 10:102-14. [PMID: 24322649 DOI: 10.1038/nrendo.2013.246] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In patients with neuroendocrine tumours (NETs), a combination of morphological imaging and nuclear medicine techniques is mandatory for primary tumour visualization, staging and evaluation of somatostatin receptor status. CT and MRI are well-suited for discerning small lesions that might escape detection by single photon emission tomography (SPECT) or PET, as well as for assessing the local invasiveness of the tumour or the response to therapy. Somatostatin receptor imaging, by (111)In-pentetreotide scintigraphy or PET with (68)Ga-labelled somatostatin analogues, frequently identifies additional lesions that are not visible on CT or MRI scans. Currently, somatostatin receptor scintigraphy with (111)In-pentetreotide is the more frequently available of the two techniques to determine somatostatin receptor expression and is needed to select patients for peptide receptor radionuclide therapy. In the future, because of its higher sensitivity, PET with (68)Ga-labelled somatostatin analogues is expected to replace somatostatin receptor scintigraphy. Whereas (18)F-FDG-PET is only used in high-grade neuroendocrine cancers, PET-CT with (18)F-dihydroxy-L-phenylalanine or (11)C-5-hydroxy-L-tryptophan is a useful problem-solving tool and could be considered for the evaluation of therapy response in the future. This article reviews the role of imaging for the diagnosis and management of intestinal and pancreatic NETs. Response evaluation and controversies in NET imaging will also be discussed.
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Affiliation(s)
- Martijn van Essen
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Anders Sundin
- Department of Radiology, Karolinska University Hospital, Stockholm, 17176 Stockholm, Sweden
| | - Eric P Krenning
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Dik J Kwekkeboom
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
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Attili F, Capurso G, Vanella G, Fuccio L, Delle Fave G, Costamagna G, Larghi A. Diagnostic and therapeutic role of endoscopy in gastroenteropancreatic neuroendocrine neoplasms. Dig Liver Dis 2014; 46:9-17. [PMID: 23731843 DOI: 10.1016/j.dld.2013.04.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Accepted: 04/20/2013] [Indexed: 02/08/2023]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms have substantially increased over the last decades. Because of the indolent clinical course of the disease even in advance stages and the rise in the incidental diagnosis of small asymptomatic lesions, the prevalence of gastroenteropancreatic neuroendocrine neoplasms is higher than that of pancreatic, gastric and oesophageal adenocarcinomas, making them the second most prevalent cancer type of the gastrointestinal tract. This increase in the overall prevalence of gastroenteropancreatic neuroendocrine neoplasms has been paralleled by a growth in the importance of the endoscopist in the care of these patients, who usually require a multidisciplinary approach. In this manuscript the diagnostic and therapeutic role of endoscopic for gastroenteropancreatic neuroendocrine neoplasms will be reviewed.
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Affiliation(s)
- Fabia Attili
- Digestive Endoscopy Unit, Catholic University, Rome, Italy
| | - Gabriele Capurso
- Division of Digestive and Liver Disease, University La Sapienza, Rome, Italy
| | | | - Lorenzo Fuccio
- Division of Gastroenterology, S. Orsola-Malpighi Hospital, University of Bologna, Italy
| | | | | | - Alberto Larghi
- Digestive Endoscopy Unit, Catholic University, Rome, Italy.
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Velikyan I, Sundin A, Sörensen J, Lubberink M, Sandström M, Garske-Román U, Lundqvist H, Granberg D, Eriksson B. Quantitative and qualitative intrapatient comparison of 68Ga-DOTATOC and 68Ga-DOTATATE: net uptake rate for accurate quantification. J Nucl Med 2013; 55:204-10. [PMID: 24379222 DOI: 10.2967/jnumed.113.126177] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
UNLABELLED Quantitative imaging and dosimetry are crucial for individualized treatment during peptide receptor radionuclide therapy (PRRT). (177)Lu-DOTATATE and (68)Ga-DOTATOC/(68)Ga-DOTATATE are used, respectively, for PRRT and PET examinations targeting somatostatin receptors (SSTRs) in patients affected by neuroendocrine tumors. The aim of the study was to quantitatively and qualitatively compare the performance of (68)Ga-DOTATOC and (68)Ga-DOTATATE in the context of subsequent PRRT with (177)Lu-DOTATATE under standardized conditions in the same patient as well as to investigate the sufficiency of standardized uptake value (SUV) for estimation of SSTR expression. METHODS Ten patients with metastatic neuroendocrine tumors underwent one 45-min dynamic and 3 whole-body PET/CT examinations at 1, 2, and 3 h after injection with both tracers. The number of detected lesions, SUVs in lesions and normal tissue, total functional tumor volume, and SSTR volume (functional tumor volume multiplied by mean SUV) were investigated for each time point. Net uptake rate (Ki) was calculated according to the Patlak method for 3 tumors per patient. RESULTS There were no significant differences in lesion count, lesion SUV, Ki, functional tumor volume, or SSTR volume between (68)Ga-DOTATOC and (68)Ga-DOTATATE at any time point. The detection rate was similar, although with differences for single lesions in occasional patients. For healthy organs, marginally higher uptake of (68)Ga-DOTATATE was observed in kidneys, bone marrow, and liver at 1 h. (68)Ga-DOTATOC uptake was higher in mediastinal blood pool at the 1-h time point (P = 0.018). The tumor-to-liver ratio was marginally higher for (68)Ga-DOTATOC at the 3-h time point (P = 0.037). Blood clearance was fast and similar for both tracers. SUV did not correlate with Ki linearly and achieved saturation for a Ki of greater than 0.2 mL/cm(3)/min, corresponding to an SUV of more than 25. CONCLUSION (68)Ga-DOTATOC and (68)Ga-DOTATATE are suited equally well for staging and patient selection for PRRT with (177)Lu-DOTATATE. However, the slight difference in the healthy organ distribution and excretion may render (68)Ga-DOTATATE preferable. SUV did not correlate linearly with Ki and thus may not reflect the SSTR density accurately at its higher values, whereas Ki might be the outcome measure of choice for quantification of SSTR density and assessment of treatment outcome.
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Affiliation(s)
- Irina Velikyan
- PET and Nuclear Medicine, Department of Radiology, Oncology, and Radiation Science, Uppsala University, Uppsala, Sweden
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Velikyan I. Prospective of ⁶⁸Ga-radiopharmaceutical development. Theranostics 2013; 4:47-80. [PMID: 24396515 PMCID: PMC3881227 DOI: 10.7150/thno.7447] [Citation(s) in RCA: 250] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Accepted: 10/01/2013] [Indexed: 01/29/2023] Open
Abstract
Positron Emission Tomography (PET) experienced accelerated development and has become an established method for medical research and clinical routine diagnostics on patient individualized basis. Development and availability of new radiopharmaceuticals specific for particular diseases is one of the driving forces of the expansion of clinical PET. The future development of the ⁶⁸Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of ⁶⁸Ga, automation of the radiopharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies for improved quantitation accuracy, PET radiopharmaceutical regulations as well as advances in radiopharmaceutical chemistry. The review presents the prospects of the ⁶⁸Ga-based radiopharmaceutical development on the basis of the current status of these aspects as well as wide range and variety of imaging agents.
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Affiliation(s)
- Irina Velikyan
- 1. Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, SE-75183 Uppsala, Sweden
- 2. PET-Centre, Centre for Medical Imaging, Uppsala University Hospital, SE-75185, Uppsala, Sweden
- 3. Department of Radiology, Oncology, and Radiation Science, Uppsala University, SE-75285 Uppsala, Sweden
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Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2013; 40:1770-80. [PMID: 23873003 DOI: 10.1007/s00259-013-2482-z] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 06/03/2013] [Indexed: 12/14/2022]
Abstract
PURPOSE Neuroendocrine tumours (NET) are uncommon and may be localized in many different places in the body. Traditional imaging has mainly been performed with CT and somatostatin receptor scintigraphy (SRS). Recently, it has become possible to use somatostatin receptor PET/CT (SMSR PET) instead, which might improve diagnostic quality. To evaluate the diagnostic quality of SMSR PET we performed a meta-analysis as an update of a previous study published in 2012. METHODS A literature search was performed searching MEDLINE, Embase and five other databases with a combination of the expressions "PET", "positron emission tomography", "neuroendocrine" and "NET". The search was updated to 31 December 2012. Studies were selected which evaluated the sensitivity and specificity of SMSR PET for NET in the thorax or abdomen with a study size of at least eight patients. The methodological quality of the included studies was evaluated with QUADAS-2. RESULTS Eight studies fulfilled the inclusion criteria and were selected for final analysis, and 14 articles from a previous meta-analysis were added for a total of 22 articles. A total of 2,105 patients were included in the studies, an increase from 567 in the previous meta-analysis. The pooled sensitivity was 93 % (95 % CI 91 - 94 %) and specificity 96 % (95 % CI 95 - 98 %). The area under the summary ROC curve was 0.98 (95 % CI 0.95 - 1.0). In the previous meta-analysis the pooled sensitivity was 93 % (95 % CI 91 - 95 %) and specificity 91 % (95 % CI 82 - 97 %). CONCLUSION SMSR PET has good diagnostic performance for evaluation of NET in the thorax and abdomen, better than SRS which has been the previous standard method. This meta-analysis gives further support for switching to SMSR PET.
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Taieb D, Legmann P, Prat F, Chevallier P, Tenenbaum F. Topographic diagnosis: Respective roles of morphological and functional imaging. ANNALES D'ENDOCRINOLOGIE 2013; 74:185-90. [DOI: 10.1016/j.ando.2013.05.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Treglia G, Castaldi P, Villani MF, Perotti G, Filice A, Ambrosini V, Cremonini N, Versari A, Fanti S, Giordano A, Rufini V. Comparison of different positron emission tomography tracers in patients with recurrent medullary thyroid carcinoma: our experience and a review of the literature. Recent Results Cancer Res 2013; 194:385-93. [PMID: 22918771 DOI: 10.1007/978-3-642-27994-2_21] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Several morphological and functional imaging techniques are usually used to detect residual/recurrent medullary thyroid carcinoma (MTC) with variable results; currently, there is growing interest in positron emission tomography (PET) methodology. Herein, we report our experience of and a literature review about the comparison of different positron emission tomography (PET) tracers in patients with residual/recurrent MTC. (18)F-DOPA PET/CT seems to be the most useful imaging method to detect recurrent MTC lesions, performing better than (18)F-FDG and (68)Ga-somatostatin analogs PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with aggressive tumors. (68)Ga-somatostatin analogs PET/CT may be useful to select patients who could benefit from radioreceptor therapy. The information provided by the various PET tracers reflects different metabolic pathways, and may help to select the most appropriate treatment.
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Affiliation(s)
- Giorgio Treglia
- Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Rome, Italy.
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Naswa N, Sharma P, Soundararajan R, Karunanithi S, Nazar AH, Kumar R, Malhotra A, Bal C. Diagnostic performance of somatostatin receptor PET/CT using 68Ga-DOTANOC in gastrinoma patients with negative or equivocal CT findings. ABDOMINAL IMAGING 2013; 38:552-560. [PMID: 22743840 DOI: 10.1007/s00261-012-9925-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
PURPOSE Contrast-enhanced CT (CECT) is a standard investigative procedure in the localization of gastrinomas. Small tumors are often missed and metastatic lesions may remain occult on CT. The purpose of present study was to prospectively evaluate the diagnostic performance of (68)Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-Octreotide ((68)Ga-DOTANOC) positron emission tomography/computed tomography (PET/CT) in gastrinoma patients with negative or equivocal CT findings. METHODS Twenty-five patients (age 46.6 ± 13.3 years; male 60%) with clinical/biochemical diagnosis of gastrinoma and negative or equivocal findings on CECT were prospectively evaluated. All of them underwent (68)Ga-DOTANOC PET/CT which was evaluated by two nuclear medicine physicians in consensus. Combination of histopathology, serum gastrin, endoscopy, and follow-up imaging were taken as reference standard. RESULTS (68)Ga-DOTANOC PET/CT was positive in 17 patients and negative in 8 patients, yielding an overall detection rate of 68%. It was positive 13/20 patients who underwent baseline evaluation and in 4/5 post-treatment patients. Of the 11 patients who had a negative CT result, (68)Ga-DOTANOC PET/CT was positive in four cases (detection rate 36.4%), while it was abnormal in 13/14 patients who had equivocal CT findings (detection rate 92.8%). Diagnostic performance of (68)Ga-DOTANOC PET/CT was superior in patients with equivocal CECT findings than that in patients with negative CECT (P = 0.010). CONCLUSION (68)Ga-DOTANOC PET/CT appears to be useful in patients with gastrinoma with negative or equivocal results on CECT, especially the latter group.
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Affiliation(s)
- Niraj Naswa
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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Rufini V, Baum RP, Castaldi P, Treglia G, De Gaetano AM, Carreras C, Kaemmerer D, Hommann M, Hörsch D, Bonomo L, Giordano A. Role of PET/CT in the functional imaging of endocrine pancreatic tumors. ACTA ACUST UNITED AC 2013; 37:1004-20. [PMID: 22422069 DOI: 10.1007/s00261-012-9871-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns ((18)F-DOPA and (11)C-5-HTP) or specific receptor expression ((68)Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of (18)F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, (11)C-5-HTP performs better than (18)F-DOPA even though its use is hampered by its complex production and limited availability and experience; (68)Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, (68)Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy.
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Affiliation(s)
- Vittoria Rufini
- Department of Bioimaging and Radiological Sciences, Institute of Nuclear Medicine, Agostino Gemelli Hospital, Università Cattolica del Sacro Cuore, Roma, Italy.
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Comparison of abdominal MRI with diffusion-weighted imaging to 68Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas. Eur J Nucl Med Mol Imaging 2013; 40:897-907. [PMID: 23460395 DOI: 10.1007/s00259-013-2371-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2012] [Accepted: 02/07/2013] [Indexed: 12/30/2022]
Abstract
PURPOSE The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and (68)Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. METHODS Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar's test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student's t test. RESULTS Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05). The mean ADC value of NET (1.02 ± 0.26 × 10(-3) mm(2)/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 ± 0.39 × 10(-3) mm(2)/s). CONCLUSION DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. (68)Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET.
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Jadvar H. Hepatocellular carcinoma and gastroenteropancreatic neuroendocrine tumors: potential role of other positron emission tomography radiotracers. Semin Nucl Med 2013; 42:247-54. [PMID: 22681673 DOI: 10.1053/j.semnuclmed.2012.02.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
18F-Fluorodeoxyglucose avidity for gastroenteropancreatic neuroendocrine tumors and hepatocellular carcinoma is variable, depending on the underlying tumor biology. Experience with non-fluorodeoxyglucose (FDG) tracers (eg, 18F-labeled amine precursors l-dihydroxyphenylalanine and 68Ga-DOTA-peptides for gastroenteropancreatic neuroendocrine tumors and radiolabeled acetate or choline for hepatocellular carcinoma) is evolving and expanding rapidly. This article reviews the role of FDG and non-FDG radiotracers in the imaging evaluation of patients with gastroenteropancreatic neuroendocrine tumors or hepatocellular carcinoma.
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Affiliation(s)
- Hossein Jadvar
- Division of Nuclear Medicine, Department of Radiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.
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Abstract
Development of new radiopharmaceuticals and their availability are crucial factors influencing the expansion of clinical nuclear medicine. The number of new (68)Ga-based imaging agents for positron emission tomography (PET) is increasing greatly. (68)Ga has been used for labeling of a broad range of molecules (small organic molecules, peptides, proteins, and oligonucleotides) as well as particles, thus demonstrating its potential to become a PET analog of the legendary generator-produced gamma-emitting (99m)Tc but with added value of higher sensitivity and resolution as well as quantitation and dynamic scanning. Further, the availability of technology for GMP-compliant automated tracer production can facilitate the introduction of new radiopharmaceuticals and enable standardized, harmonized multicenter studies to be conducted for regulatory approval. This chapter presents some examples of tracers for targeted, pretargeted, and nontargeted imaging with emphasis on the potential of (68)Ga to facilitate clinically practical PET development and to promote the PET technique worldwide for earlier and better diagnostics, and personalized medicine with the ultimate objective of improved therapeutic outcome.
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Affiliation(s)
- Irina Velikyan
- Department of Radiology, Uppsala University, Uppsala, Sweden.
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Shrikhande SV, Sirohi B, Goel M, Barreto SG. Pancreatic neuroendocrine tumors. Indian J Gastroenterol 2013; 32:3-17. [PMID: 23054950 DOI: 10.1007/s12664-012-0257-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 09/04/2012] [Indexed: 02/04/2023]
Abstract
Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.
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Affiliation(s)
- Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, India.
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Sahani DV, Bonaffini PA, Catalano OA, Guimaraes AR, Blake MA. State-of-the-art PET/CT of the pancreas: current role and emerging indications. Radiographics 2012; 32:1133-58; discussion 1158-60. [PMID: 22786999 DOI: 10.1148/rg.324115143] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Fused positron emission tomography (PET)/computed tomography (CT) is a recently developed technology that couples the functional information of PET with the anatomic details of CT. Integrated PET/CT scanners produce both PET and contrast material-enhanced CT images of the entire body in one setting. Typically, the amount of fluorine 18 (18F) fluorodeoxyglucose (FDG) uptake in normal pancreatic parenchyma is insignificant compared with that of the liver. However, both malignant (eg, adenocarcinoma) and benign (eg, acute pancreatitis) pancreatic conditions may demonstrate intense FDG uptake. PET/CT provides an opportunity to depict pancreatic tumors and distant metastases, perform preoperative staging, and monitor response to treatment, and it has proved useful in distinguishing postoperative fibrosis from recurrence. In selected cases, PET/CT findings may be used to help diagnose autoimmune pancreatitis mimicking a mass by depicting systemic involvement. PET/CT may also be used to direct biopsy to sites more likely to yield representative tumor tissue. Novel radiolabeled molecules, such as sigma-receptor ligands and 18F-3'-fluoro-3'-deoxy-l-thymidine (FLT), may play an even greater role in distinguishing tumor recurrence from postoperative fibrosis or inflammation.
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Affiliation(s)
- Dushyant V Sahani
- Department of Radiology, Division of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, White 270, Boston, MA 02114, USA.
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Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 2012; 26:803-18. [PMID: 23582920 DOI: 10.1016/j.bpg.2012.12.004] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023]
Abstract
Neuroendocrine tumours (NETs) comprise a heterogeneous group of neoplasms with very varying clinical expression. A functioning NET, for instance in the pancreas, may be very small and yet give rise to severe endocrine symptoms whereas a patient with a small bowel tumour may present with diffuse symptoms and disseminated disease with a palpable bulky liver. Imaging of NETs is therefore challenging and the imaging needs in the various patients are diverse. The basic modalities for NET imaging are computed tomography (CT) or magnetic resonance imaging (MRI) in combination with somatostatin receptor imaging (SMI) by scintigraphy with 111In-labelled octreotide (OctreoScan) or more recently by positron emission tomography (PET) with 68Ga-labelled somatostatin analogues. In this review these various morphological and functional imaging modalities and important methodological aspects are described. Imaging requirements for the various types of NETs are discussed and typical image findings are illustrated.
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Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience. JOURNAL OF ONCOLOGY 2012; 2012:320198. [PMID: 22934111 PMCID: PMC3425839 DOI: 10.1155/2012/320198] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Revised: 06/25/2012] [Accepted: 06/26/2012] [Indexed: 12/14/2022]
Abstract
The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33–83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using 68Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq (90Y-DOTATOC/DOTATATE) or 6.0 GBq (177Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%).
Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.
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Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine 2012; 42:80-7. [PMID: 22350660 DOI: 10.1007/s12020-012-9631-1] [Citation(s) in RCA: 186] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2011] [Accepted: 02/07/2012] [Indexed: 02/07/2023]
Abstract
UNLABELLED Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. RESULTS Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91-95%) and 91% (95% CI: 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.
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Affiliation(s)
- Giorgio Treglia
- Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Largo Gemelli, 8, 00168, Rome, Italy.
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Sahani DV, Guimaraes AR, Blake MA, Bonaffini PA, Catalano OA. Author’s Response. Radiographics 2012. [DOI: 10.1148/radiographics.32.4.3241160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging 2012; 39:569-80. [PMID: 22223169 DOI: 10.1007/s00259-011-2031-6] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Accepted: 12/08/2011] [Indexed: 10/14/2022]
Abstract
PURPOSE To retrospectively evaluate and compare (18)F-FDG, (18)F-DOPA and (68)Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. METHODS Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. RESULTS At least one focus of abnormal uptake was observed on PET/CT in 13 patients with (18)F-DOPA (72.2% sensitivity), in 6 patients with (68)Ga-somatostatin analogues (33.3%) and in 3 patients with (18)F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between (18)F-DOPA and (18)F-FDG PET/CT (p < 0.01) and between (18)F-DOPA and (68)Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. (18)F-DOPA PET/CT detected 85% of lesions (61 of 72), (68)Ga-somatostatin analogue PET/CT 20% (14 of 72) and (18)F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by (18)F-DOPA PET/CT and (18)F-FDG PET/CT (p < 0.01 for all the analyses) and by (18)F-DOPA PET/CT and (68)Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). CONCLUSION (18)F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than (18)F-FDG and (68)Ga-somatostatin analogue PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with an aggressive tumour.
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Owens MM. Walk closer or carry big glass? Comparing EUS and multidetector CT. Gastrointest Endosc 2011; 73:697-9. [PMID: 21457814 DOI: 10.1016/j.gie.2010.10.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2010] [Accepted: 10/28/2010] [Indexed: 02/08/2023]
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Detection of recurrent pancreatic primitive neuroectodermal tumor by tc-99m hydrazinonicotinyl-tyr3-octreotide scan. Clin Nucl Med 2011; 36:54-5. [PMID: 21157213 DOI: 10.1097/rlu.0b013e3181feeffa] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
A 24-year-old asymptomatic female with a history of exophytic primitive neuroectodermal tumor in the uncinate process of the pancreas was evaluated by Tc-99m hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) imaging as a part of the routine check-up. The images revealed focally increased activity in the head of the pancreas, indicating possible recurrent tumor. However, the results of all examinations considered, especially because of negative results from anatomic imaging, the finding from the HYNIC-TOC scan was regarded as likely false positive, and no new actions were taken. Eighteen months later, the patient developed abdominal mass. Repeat HYNIC-TOC imaging redemonstrated the focus of abnormal activity, which was confirmed as recurrent primitive neuroectodermal tumor pathologically.
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Lips N, Deroose CM, Bielen D, Bossuyt P, Mortelmans L. Wandering spleen on a 68Ga-DOTATOC-PET/CT scan. Eur J Nucl Med Mol Imaging 2011; 38:982. [PMID: 21229243 DOI: 10.1007/s00259-010-1714-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Accepted: 12/16/2010] [Indexed: 11/24/2022]
Affiliation(s)
- Nele Lips
- Department of Nuclear Medicine, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
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