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Yokoyama K, Matsuki M, Isozaki T, Ito K, Imokawa T, Ozawa A, Kimura K, Tsuchiya J, Tateishi U. Advances in multimodal imaging for adrenal gland disorders: integrating CT, MRI, and nuclear medicine. Jpn J Radiol 2025; 43:903-926. [PMID: 39794659 DOI: 10.1007/s11604-025-01732-6] [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: 11/16/2024] [Accepted: 01/03/2025] [Indexed: 01/13/2025]
Abstract
Adrenal diseases pose significant diagnostic challenges due to the wide range of neoplastic and non-neoplastic pathologies. Radiologists have a crucial role in diagnosing and managing these conditions by, leveraging advanced imaging techniques. This review discusses the vital role of computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine in adrenal imaging, and focuses on morphological and functional evaluations. First, the anatomy and physiology of the adrenal glands are described, followed by a discussion on ectopic adrenocortical adenomas and how they develop. The concepts and imaging findings of congenital diseases, such as congenital adrenal hyperplasia (CAH), adrenal rest tumors, and adrenocortical nodular disease, considering recent updates to the WHO Classification of Tumours (5th ed.) terminology are highlighted. The diagnostic value of dynamic contrast-enhanced CT and chemical-shift MRI for identifying adrenocortical adenomas are emphasized, alongside the use of adrenocortical scintigraphy such as 131I-adosterol scintigraphy for diagnosing Cushing's disease, Cushing's syndrome (CS), subclinical CS, and ectopic adrenocorticotropic hormone-producing tumors. Systemic complications associated with CS, and the diagnosis and treatment of pheochromocytomas, paragangliomas (PPGLs), and neuroblastomas, will also be discussed focusing on 123I-metaiodobenzylguanidine (MIBG) imaging and 131I-MIBG therapy. Pitfalls in 123I-MIBG imaging and the increasing importance of diagnosing hereditary PPGLs due to increased genetic testing are also be discussed. Additionally, the broad differential diagnosis for adrenal masses-including malignancies like adrenal carcinoma, metastases, and malignant lymphoma, as well as benign conditions like myelolipoma and ganglioneuroma, and complications, such as adrenal hemorrhage, infarction, and infections-will be outlined. The goal of this review was to provide an overview of adrenal diseases that includes the most recent information for radiologists to stay updated on the latest imaging techniques and advancements that can ensure accurate diagnosis and effective management.
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Affiliation(s)
- Kota Yokoyama
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan.
| | - Mitsuru Matsuki
- Department of Pediatric Medical Imaging, Jichi Children's Medical Center Tochigi, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Takanori Isozaki
- Department of Radiology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Kimiteru Ito
- Department of Radiology, National Cancer Center, Tokyo, Japan
| | - Tomoki Imokawa
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Akane Ozawa
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Koichiro Kimura
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Tsuchiya
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Ukihide Tateishi
- Department of Diagnostic Radiology, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan
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Hirahara M, Nakajo M, Kitazano I, Jinguji M, Tani A, Takumi K, Kamimura K, Tanimoto A, Yoshiura T. Usefulness of the Primary Tumor Standardized Uptake Value of Iodine-123 Metaiodobenzylguanidine for Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma. Mol Imaging Biol 2024; 26:1005-1015. [PMID: 39294365 PMCID: PMC11635048 DOI: 10.1007/s11307-024-01952-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/15/2024] [Accepted: 09/01/2024] [Indexed: 09/20/2024]
Abstract
PURPOSE To examine the usefulness of semi-quantitative analysis using the standardized uptake value (SUV) of iodine-123 metaiodobenzylguanidine ([123I]-MIBG) for predicting metastatic potential in patients with pheochromocytoma (PHEO) and paraganglioma (PGL). PROCEDURES This study included 18 PHEO and 2 PGL patients. [123I]-MIBG visibility and SUV-related parameters (SUVmax, SUVmean, tumor volume of [123I]-MIBG uptake [TV_MIBG], and total lesion [123I]-MIBG uptake) were compared with the pathological grading obtained using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP), which are used to predict metastatic potential. The PASS scores were categorized as < 4 and ≥ 4. Based on the GAPP scores, PHEOs/PGLs were categorized as follows: well, moderately, and poorly differentiated tumors. The Mann-Whitney U test or Spearman's rank correlation was used to assess differences or associations between two quantitative variables. RESULTS All PHEOs/PGLs were visualized on [123I]-MIBG scintigraphy. There were 16 PASS < 4 and 4 PASS ≥ 4 tumors. Moreover, 11 and 9 tumors were well and moderately differentiated, respectively. The uptake scores and SUV-related parameters significantly differed between tumors with a PASS score of < 4 and those with a PASS score of ≥ 4 (each, p > 0.05). Moderately differentiated tumors had significantly higher uptake scores and SUV-related parameters except TV_MIBG than well-differentiated tumors (each, p < 0.05). The GAPP score was positively correlated with the uptake scores and SUV-related parameters (each, p < 0.05) except TV_MIBG. CONCLUSIONS The primary tumor [123I]-MIBG uptake assessed using SUV-related parameters can be an imaging tool for predicting metastatic potential in patients with PHEO/PGL.
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Affiliation(s)
- Mitsuho Hirahara
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Masatoyo Nakajo
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
| | - Ikumi Kitazano
- Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Megumi Jinguji
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Atsushi Tani
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Koji Takumi
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Kiyohisa Kamimura
- Department of Advanced Radiological Imaging, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Akihide Tanimoto
- Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Takashi Yoshiura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Chang MC, Peng CL, Chen CT, Shih YH, Chen JH, Tai YJ, Chiang YC. Iodine-123 Metaiodobenzylguanidine (I-123 MIBG) in Clinical Applications: A Comprehensive Review. Pharmaceuticals (Basel) 2024; 17:1563. [PMID: 39770405 PMCID: PMC11676292 DOI: 10.3390/ph17121563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 01/06/2025] Open
Abstract
Iodine-123 metaiodobenzylguanidine (I-123 MIBG) is a crucial radiopharmaceutical widely used in nuclear medicine for its diagnostic capabilities in both cardiology and oncology. This review aims to present a comprehensive evaluation of the clinical applications of I-123 MIBG, focusing on its use in diagnosing and managing various diseases. In cardiology, I-123 MIBG has proven invaluable in assessing cardiac sympathetic innervation, particularly in patients with heart failure, where it provides prognostic information that guides treatment strategies. In oncology, I-123 MIBG is primarily utilized for imaging neuroendocrine tumors, such as neuroblastoma and pheochromocytoma, where it offers high specificity and sensitivity in the detection of adrenergic tissue. Additionally, its role in neurology, specifically in differentiating between Parkinson's disease, dementia, and Lewy body dementia, has become increasingly significant due to its ability to identify postganglionic sympathetic dysfunction. Despite its established clinical utility, the use of I-123 MIBG is not without limitations, including variability in imaging protocols and interpretation challenges. This review will explore these issues and discuss emerging alternatives, while also highlighting areas where I-123 MIBG continues to be a gold standard. By synthesizing the current research, this article aims to provide a clear understanding of the strengths, limitations, and prospects of I-123 MIBG in clinical practice.
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Affiliation(s)
- Ming-Cheng Chang
- Department of Isotope Research Application, National Atomic Research Institute, Taoyuan 325207, Taiwan; (M.-C.C.); (C.-L.P.); (C.-T.C.); (Y.-H.S.); (J.-H.C.)
| | - Cheng-Liang Peng
- Department of Isotope Research Application, National Atomic Research Institute, Taoyuan 325207, Taiwan; (M.-C.C.); (C.-L.P.); (C.-T.C.); (Y.-H.S.); (J.-H.C.)
| | - Chun-Tang Chen
- Department of Isotope Research Application, National Atomic Research Institute, Taoyuan 325207, Taiwan; (M.-C.C.); (C.-L.P.); (C.-T.C.); (Y.-H.S.); (J.-H.C.)
| | - Ying-Hsia Shih
- Department of Isotope Research Application, National Atomic Research Institute, Taoyuan 325207, Taiwan; (M.-C.C.); (C.-L.P.); (C.-T.C.); (Y.-H.S.); (J.-H.C.)
| | - Jyun-Hong Chen
- Department of Isotope Research Application, National Atomic Research Institute, Taoyuan 325207, Taiwan; (M.-C.C.); (C.-L.P.); (C.-T.C.); (Y.-H.S.); (J.-H.C.)
| | - Yi-Jou Tai
- Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100226, Taiwan
| | - Ying-Cheng Chiang
- Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100226, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu 302058, Taiwan
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Singh K, Sandler G, Hahn D, Chung DK. Comparison of 68 Ga-DOTATATE PET/CT and 123 I-MIBG SPECT/CT in the Imaging of Functional Pheochromocytoma in an Adolescent Patient With Von Hippel-Lindau Syndrome. Clin Nucl Med 2024; 49:e451-e452. [PMID: 38861407 DOI: 10.1097/rlu.0000000000005308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2024]
Abstract
ABSTRACT A 17-year-old boy with Von Hippel-Lindau syndrome presented with hypertension, raised plasma catecholamines, and MRI findings of a new pancreatic tail lesion and 2 stable right adrenal lesions concerning for functional neuroendocrine tumors. A 68 Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123 I-MIBG SPECT/CT study demonstrated high-grade tracer uptake within the adrenal lesions, with no significant uptake appreciated in the pancreatic lesion. The adrenal lesions were resected, and pathology was consistent with pheochromocytoma. Plasma catecholamines returned to within the normal range and hypertension resolved.
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Affiliation(s)
| | | | - Deirdre Hahn
- Nephrology, The Children's Hospital at Westmead, Westmead, Australia
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Hung WT, Liu CJ, Liu YL, Ko KY, Chou SW, Chang HH, Yang YL, Lu MY, Hsu WM. Feasibility of 18F-DOPA and 18F-FDG PET/CT for guiding decision-making for localized incidental neuroblastoma in infants under 18 months of age. Pediatr Blood Cancer 2024; 71:e30983. [PMID: 38605509 DOI: 10.1002/pbc.30983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 02/27/2024] [Accepted: 03/18/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.
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Affiliation(s)
- Wan-Ting Hung
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chia-Ju Liu
- Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Lin Liu
- Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University and Taipei Medical University Hospital, Taipei, Taiwan
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Kuan-Yin Ko
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Nuclear Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Shu-Wei Chou
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Hao Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Yung-Li Yang
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Meng-Yao Lu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Ming Hsu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
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Timmers HJLM, Taïeb D, Pacak K, Lenders JWM. Imaging of Pheochromocytomas and Paragangliomas. Endocr Rev 2024; 45:414-434. [PMID: 38206185 PMCID: PMC11074798 DOI: 10.1210/endrev/bnae001] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 12/11/2023] [Accepted: 01/10/2024] [Indexed: 01/12/2024]
Abstract
Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
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Affiliation(s)
- Henri J L M Timmers
- Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
| | - David Taïeb
- Department of Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France and European Center for Research in Medical Imaging, Aix-Marseille University, 13005 Marseille, France
| | - Karel Pacak
- Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1583, USA
| | - Jacques W M Lenders
- Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
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Lawal IO, Abubakar SO, Ndlovu H, Mokoala KMG, More SS, Sathekge MM. Advances in Radioligand Theranostics in Oncology. Mol Diagn Ther 2024; 28:265-289. [PMID: 38555542 DOI: 10.1007/s40291-024-00702-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2024] [Indexed: 04/02/2024]
Abstract
Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (177Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved 177Lu-DOTATATE and 177Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.
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Affiliation(s)
- Ismaheel O Lawal
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, NE, Atlanta, GA, 30322, USA.
- Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa.
| | - Sofiullah O Abubakar
- Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman
| | - Honest Ndlovu
- Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, 0001, South Africa
| | - Kgomotso M G Mokoala
- Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, 0001, South Africa
| | - Stuart S More
- Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa
- Division of Nuclear Medicine, Department of Radiation Medicine, University of Cape Town, Cape Town, 7700, South Africa
| | - Mike M Sathekge
- Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa
- Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, 0001, South Africa
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Feng L, Yang X, Wang C, Zhang H, Wang W, Yang J. Predicting event-free survival after induction of remission in high-risk pediatric neuroblastoma: combining 123I-MIBG SPECT-CT radiomics and clinical factors. Pediatr Radiol 2024; 54:805-819. [PMID: 38492045 DOI: 10.1007/s00247-024-05901-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 02/29/2024] [Accepted: 03/02/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND Accurately quantifying event-free survival after induction of remission in high-risk neuroblastoma can lead to better subsequent treatment decisions, including whether more aggressive therapy or milder treatment is needed to reduce unnecessary treatment side effects, thereby improving patient survival. OBJECTIVE To develop and validate a 123I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography-computed tomography (SPECT-CT)-based radiomics nomogram and evaluate its value in predicting event-free survival after induction of remission in high-risk neuroblastoma. MATERIALS AND METHODS One hundred and seventy-two patients with high-risk neuroblastoma who underwent an 123I-MIBG SPECT-CT examination were retrospectively reviewed. Eighty-seven patients with high-risk neuroblastoma met the final inclusion and exclusion criteria and were randomized into training and validation cohorts in a 7:3 ratio. The SPECT-CT images of patients were visually analyzed to assess the Curie score. The 3D Slicer software tool was used to outline the region of interest of the lumbar 3-5 vertebral bodies on the SPECT-CT images. Radiomics features were extracted and screened, and a radiomics model was constructed with the selected radiomics features. Univariate and multivariate Cox regression analyses were used to determine clinical risk factors and construct the clinical model. The radiomics nomogram was constructed using multivariate Cox regression analysis by incorporating radiomics features and clinical risk factors. C-index and time-dependent receiver operating characteristic curves were used to evaluate the performance of the different models. RESULTS The Curie score had the lowest efficacy for the assessment of event-free survival, with a C-index of 0.576 and 0.553 in the training and validation cohorts, respectively. The radiomics model, constructed from 11 radiomics features, outperformed the clinical model in predicting event-free survival in both the training cohort (C-index, 0.780 vs. 0.653) and validation cohort (C-index, 0.687 vs. 0.667). The nomogram predicted the best prognosis for event-free survival in both the training and validation cohorts, with C-indices of 0.819 and 0.712, and 1-year areas under the curve of 0.899 and 0.748, respectively. CONCLUSION 123I-MIBG SPECT-CT-based radiomics can accurately predict the event-free survival of high-risk neuroblastoma after induction of remission The constructed nomogram may enable an individualized assessment of high-risk neuroblastoma prognosis and assist clinicians in optimizing patient treatment and follow-up plans, thereby potentially improving patient survival.
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Affiliation(s)
- Lijuan Feng
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China
| | - Xu Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China
| | - Chao Wang
- SinoUnion Healthcare Inc, Beijing, China
| | - Hui Zhang
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Wei Wang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China
| | - Jigang Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China.
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Kobayashi A, Ishinoda Y, Uto A, Ogata S, Oshima N. A Case of Pheochromocytoma With Coagulation Necrosis Due to Hypertensive Crisis Aggravated by Contrast-Enhanced CT Scan and Negative 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy. Cureus 2024; 16:e56878. [PMID: 38659567 PMCID: PMC11040423 DOI: 10.7759/cureus.56878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2024] [Indexed: 04/26/2024] Open
Abstract
123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy is a highly sensitive and specific imaging test for the diagnosis of pheochromocytoma. Typical pheochromocytomas are positive on 123I-MIBG scintigraphy; however, cases of paragangliomas eliciting negative results have been reported. We encountered a case of hypertensive crisis resulting in extensive coagulative necrosis of a pheochromocytoma and negative findings on 123I-MIBG scintigraphy. A 50-year-old Japanese female presented with an acute onset of vomiting, epigastralgia, and abdominal pain. Immediately after contrast-enhanced CT, the patient developed respiratory failure and was intubated. The CT scan revealed a 5-cm left adrenal mass, and a pheochromocytoma crisis was suspected. The patient's condition stabilized following phentolamine administration. Regarding the assessment for pheochromocytoma, plasma metanephrine levels were not markedly increased, and 123I-MIBG scintigraphy was negative. However, a histological examination of the left adrenal mass revealed extensive coagulative necrosis of the entire adrenal mass, comprising trabecular and alveolar growth of large polygonal cells that were immunopositive for chromogranin A/synaptophysin, thereby suggesting a diagnosis of pheochromocytoma. There have been three reported cases of 123I-MIBG scintigraphy-negative pheochromocytomas because of pure avascular necrosis without hemorrhage or rupture. To the best of our knowledge, this is the first reported case of massive tumor necrosis due to hypertensive crisis exacerbated after contrast-enhanced CT imaging. In conclusion, pheochromocytoma cannot be ruled out even with negative findings on 123I-MIBG scintigraphy. Accordingly, clinical judgment must be made based on a comprehensive assessment of the clinical course and pathological diagnosis, especially for cases involving a hypertensive crisis.
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Affiliation(s)
- Ai Kobayashi
- Department of Endocrinology, National Defense Medical College, Saitama, JPN
| | - Yuki Ishinoda
- Department of Endocrinology, National Defense Medical College, Saitama, JPN
| | - Asuka Uto
- Department of Endocrinology, National Defense Medical College, Saitama, JPN
| | - Sho Ogata
- Department of Laboratory Medicine, National Defense Medical College, Saitama, JPN
| | - Naoki Oshima
- Department of Nephrology, National Defense Medical College, Saitama, JPN
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Feng L, Li S, Wang C, Yang J. Current Status and Future Perspective on Molecular Imaging and Treatment of Neuroblastoma. Semin Nucl Med 2023; 53:517-529. [PMID: 36682980 DOI: 10.1053/j.semnuclmed.2022.12.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/02/2022] [Accepted: 12/15/2022] [Indexed: 01/22/2023]
Abstract
Neuroblastoma is the most common extracranial solid tumor in children and arises from anywhere along the sympathetic nervous system. It is a highly heterogeneous disease with a wide range of prognosis, from spontaneous regression or maturing to highly aggressive. About half of pediatric neuroblastoma patients develop the metastatic disease at diagnosis, which carries a poor prognosis. Nuclear medicine plays a pivotal role in the diagnosis, staging, response assessment, and long-term follow-up of neuroblastoma. And it has also played a prominent role in the treatment of neuroblastoma. Because the structure of metaiodobenzylguanidine (MIBG) is similar to that of norepinephrine, 90% of neuroblastomas are MIBG-avid. 123I-MIBG whole-body scintigraphy is the standard nuclear imaging technique for neuroblastoma, usually in combination with SPECT/CT. However, approximately 10% of neuroblastomas are MIBG nonavid. PET imaging has many technical advantages over SPECT imaging, such as higher spatial and temporal resolution, higher sensitivity, superior quantitative capability, and whole-body tomographic imaging. In recent years, various tracers have been used for imaging neuroblastoma with PET. The importance of patient-specific targeted radionuclide therapy for neuroblastoma therapy has also increased. 131I-MIBG therapy is part of the front-line treatment for children with high-risk neuroblastoma. And peptide receptor radionuclide therapy with radionuclide-labeled somatostatin analogues has been successfully used in the therapy of neuroblastoma. Moreover, radioimmunoimaging has important applications in the diagnosis of neuroblastoma, and radioimmunotherapy may provide a novel treatment modality against neuroblastoma. This review discusses the use of current and novel radiopharmaceuticals in nuclear medicine imaging and therapy of neuroblastoma.
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Affiliation(s)
- Lijuan Feng
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Siqi Li
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chaoran Wang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jigang Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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11
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Castle JT, Levy BE, Chauhan A. Pediatric Neuroendocrine Neoplasms: Rare Malignancies with Incredible Variability. Cancers (Basel) 2022; 14:cancers14205049. [PMID: 36291833 PMCID: PMC9599522 DOI: 10.3390/cancers14205049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 11/16/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be devastating if not diagnosed and treated early, however, symptoms are variable and can be indolent for many years. There is a reported median of 10 years from the appearance of the first symptoms to time of diagnosis. Considering some of these neoplasms have a mortality rate as high as 90%, it is crucial healthcare providers are aware of NENs and remain vigilant. With better provider education and easily accessible resources for information about these neoplasms, awareness can be improved leading to earlier disease recognition and diagnosis. This manuscript aims to provide an overview of both the most common NENs as well as the rarer NENs with high lethality in the pediatric population. This review provides up to date evidence and recommendations, encompassing recent changes in classification and advances in treatment modalities, including recently completed and ongoing clinical trials.
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Affiliation(s)
- Jennifer T. Castle
- Department of Surgery, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
| | - Brittany E. Levy
- Department of Surgery, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
| | - Aman Chauhan
- Department of Internal Medicine-Medical Oncology, Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA
- Correspondence: or
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12
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Production Review of Accelerator-Based Medical Isotopes. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27165294. [PMID: 36014532 PMCID: PMC9415084 DOI: 10.3390/molecules27165294] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022]
Abstract
The production of reactor-based medical isotopes is fragile, which has meant supply shortages from time to time. This paper reviews alternative production methods in the form of cyclotrons, linear accelerators and neutron generators. Finally, the status of the production of medical isotopes in China is described.
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13
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Schmidt M, Decarolis B, Franzius C, Hero B, Pfluger T, Rogasch JMM, Simon T. Durchführung und Befundung der 123I-mIBG-Szintigraphie bei Kindern und Jugendlichen mit Neuroblastom (Version 3) – DGN-Handlungsempfehlung (S1-Leitlinie), Stand: 2/2020 – AWMF-Registernummer: 031-040. Nuklearmedizin 2022; 61:96-110. [PMID: 35421899 DOI: 10.1055/a-1778-3052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfasssungDie aktualisierte 3. Fassung der 123I-mIBG-Szintigrafie bei Kindern und Jugendlichen berücksichtigt folgende aktuelle Entwicklungen: Die Leitlinie fokussiert auf die diagnostische Anwendung von 123I-mIBG beim Neuroblastom. 131I-mIBG kommt bei der Radionuklidtherapie zum Einsatz. An wenigen Stellen wird auf Besonderheiten des 131I-mIBG bei der Befundung von Posttherapie-Szintigrammen eingegangen. Es werden aktuelle Entwicklungen in der Patientenvorbereitung bei den Medikamenteninterferenzen und Empfehlungen zur Schilddrüsenblockade berücksichtigt. Neue Empfehlungen der zu applizierenden Aktivität werden genannt und die damit assoziierten Probleme diskutiert. Die Bildakquisition unter Berücksichtigung von SPECT bzw. SPECT/CT des Körperstammes inkl. des Kopfes wird berücksichtigt. Die Befundung unter Verwendung des SIOPEN-Scores wird neu aufgenommen. Auf PET bzw. PET/CT mit 18F-DOPA bzw. 68Ga-DotaTATE wird verwiesen.
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Affiliation(s)
- Matthias Schmidt
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Köln, Köln (Cologne), Germany
| | - Boris Decarolis
- Klinik und Poliklinik für Kinderheilkunde, Abteilung Kinderonkologie und -Hämatologie, Universitätsklinikum Köln, Köln (Cologne), Germany
| | - Christiane Franzius
- Zentrum für moderne Diagnostik (ZeMoDi), MR- und MR/PET, Schwachhauser Heerstraße 63 A, 28211 Bremen, ZeMoDi, Bremen, Germany
| | - Barbara Hero
- Klinik und Poliklinik für Kinderheilkunde, Abteilung Kinderonkologie und -Hämatologie, Universitätsklinikum Köln, Köln (Cologne), Germany
| | - Thomas Pfluger
- Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany
| | | | - Thorsten Simon
- Klinik und Poliklinik für Kinderheilkunde, Abteilung Kinderonkologie und -Hämatologie, Universitätsklinikum Köln, Köln (Cologne), Germany
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14
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Dong X, Meng X, Zhang T, Zhao L, Liu F, Han X, Liu Y, Zhu H, Zhou X, Miao Q, Zhang S. Diagnosis and Outcome of Cardiac Paragangliomas: A Retrospective Observational Cohort Study in China. Front Cardiovasc Med 2022; 8:780382. [PMID: 35071353 PMCID: PMC8766960 DOI: 10.3389/fcvm.2021.780382] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/05/2021] [Indexed: 11/30/2022] Open
Abstract
Background: Cardiac paragangliomas (CPGLs) are rare neuroendocrine tumors that are easily overlooked and difficult to diagnose. Detailed comprehensive data regarding CPGL diagnosis and outcome are lacking. Methods: We retrospectively analyzed a cohort of 27 CPGL patients. This cohort represents the largest such cohort reported to date. Results: The prevalence of trilogy symptoms (concurrent palpitations, hyperhidrosis, and headache) was frequent (9/27, 33.3%). Sensitivity of echocardiography and contrast-enhanced computed tomography for localization of CPGL were 81.8% and 87%, respectively. Octreotide scintigraphy showed 100% sensitivity for detecting GPCLs, while sensitivity of I131-metaiodoben-zylguanidine scintigraphy was only 32.9%. Multiple tumors were found in 29.6% of patients. Most CPGLs originated from the epicardium or root of the great vessels (92.9%) and were mostly supplied by the coronary arteries and their branches (95.7%). Twenty-four patients underwent surgical treatment. Although local invasion was present in 40.0% of patients, it did not affect long-term outcome. Mean follow-up was 6.9 ± 3.6 years. Biochemical remission was achieved in 85% of patients. The recurrence rate was 15%. Conclusions: Manifestations of CPGLs are non-specific and they can be difficult to detect on imaging examinations. Octreotide scintigraphy should be performed in patients with suspected paragangliomas to screen for multiple lesions. Surgical resection of CPGLs can achieve symptom relief and biochemical remission.
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Affiliation(s)
- Xueqi Dong
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Meng
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ting Zhang
- Department of Emergency, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Lin Zhao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fang Liu
- Department of Emergency, Puren Hospital of Beijing, Beijing, China
| | - Xu Han
- Department of Emergency, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yecheng Liu
- Department of Emergency, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- *Correspondence: Yecheng Liu
| | - Huadong Zhu
- Department of Emergency, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Huadong Zhu
| | - Xianliang Zhou
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Xianliang Zhou
| | - Qi Miao
- Department of Cardiac Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Shuyang Zhang
- Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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15
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Nyakale Elizabeth N, Kabunda J. Nuclear medicine therapy of malignant pheochromocytomas, neuroblastomas and ganglioneuromas. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00174-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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16
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Mahajan S, Pandit-Taskar N. Imaging in malignant adrenal cancers. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00149-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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17
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Xiong SC, Di XP, Zhang MN, Wu K, Li X. A rare case report of multifocal para-aortic and para-vesical paragangliomas. Front Endocrinol (Lausanne) 2022; 13:946496. [PMID: 36004346 PMCID: PMC9393499 DOI: 10.3389/fendo.2022.946496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 07/12/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Paragangliomas (PGLs) are uncommon tumors of uncertain malignant potential. Multifocal paragangliomas are scarcely reported in the literature. CASE SUMMARY A 25-year-old male patient was reported for the first time with multifocal para-aortic and para-vesical PGLs. The diagnosis was identified by blood catecholamine tests and enhanced CT scan and MIBG scintigraphy. A resection surgery was performed for treatment and the immunochemistry test of the tumors presented the features of PGL. CONCLUSION A case of multifocal para-aortic and para-vesical PGLs confirmed by the catecholamine test, enhanced CT, and MIBG scintigraphy is presented. The cooperation of experienced surgeons, anesthesiologists, and endocrinologists was critical in treatment.
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Affiliation(s)
- San-Chao Xiong
- Department of Urology, Chengdu Second People’s Hospital, Chengdu, China
| | - Xing-Peng Di
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Meng-Ni Zhang
- Department of Pathology, Institute of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Kan Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xiang Li,
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18
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Burak Z. Radionuclide Therapy in Neuroectodermal Tumors. RADIONUCLIDE THERAPY 2022:199-222. [DOI: 10.1007/978-3-030-97220-2_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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19
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Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2022:891-917. [DOI: 10.1007/978-3-031-05494-5_17] [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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20
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kacem FH, Salah A, Fathallah B, Boujelben K, Charfi N, Abid M. Presentation and management of pheochromocytomas and paragangliomas: about 40 cases. AFRICAN JOURNAL OF UROLOGY 2021. [DOI: 10.1186/s12301-021-00265-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Pheochromocytoma and paraganglioma are rare neuroendocrine tumors of the chromaffin tissue, which may produce catecholamines. The aim of our study was to analyze the clinical and para-clinical aspects as well as the therapeutic and evolutionary aspects of pheocromocytomas and paragangliomas based on a series of 40 cases.
Methods
Our retrospective population-based research study includes 40 patients. Then, a statistical analysis was carried out using the SPSS software (version21).
Results
Our study involves 40 patients, including 23 women (57, 5%) and 17 men (42,5%). The mean age at the time of the diagnosis was 43.8 ± 16.8 years. The circumstances of the discovery were mainly characterized by adrenal incidentaloma and hypertension. The biological diagnosis was based on the dosage of urinary metanephrines and plasma-free metanephrines in, respectively, 61.5% and 18% of cases. A computerized tomography scan and/or a magnetic resonance imaging scan could help to locate the tumor in 100% of cases. Our series includes 3 cases of bilateral pheochromocytoma, 3 cases of paragangliomas and 1 case of malignant pheochromocytoma, while a hereditary form was retained in 3 patients. In fact, thirty-two patients were operated; cure was clinically labeled in 100% and biologically in 87.5% of patients.
Conclusions
The main points for improvement that our study has revealed are; a patient follow-up after surgery, which was not always regular, and an insufficient screening for genetic diseases associated with pheochromocytomas and paragangliomas.
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21
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Diagnostic Value of Seven Different Imaging Modalities for Patients with Neuroblastic Tumors: A Network Meta-Analysis. CONTRAST MEDIA & MOLECULAR IMAGING 2021; 2021:5333366. [PMID: 34548851 PMCID: PMC8429030 DOI: 10.1155/2021/5333366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 11/25/2022]
Abstract
Objective We performed a systematic review and network meta-analysis (NMA) to compare the diagnostic value of seven different imaging modalities for the detection of neuroblastic tumors in diverse clinical settings. Methods PubMed, Embase, Medline, and the Cochrane Library were searched to identify eligible studies from inception to Sep 29, 2020. Quality assessment of included studies was appraised with Quality Assessment of Diagnostic Accuracy Studies. Firstly, direct pairwise meta-analysis was conducted to calculate the pooled estimates of odds ratio (OR) and 95% confidence interval (CI) of the sensitivity, specificity, NPV, PPV, and DR. Next, NMA using Bayesian methods was performed. The superiority index was assessed to quantify the rank probability of a diagnostic test. The studies performed SPECT/CT or SPECT were analyzed separately from the ones only performed planar imaging. Results A total of 1135 patients from 32 studies, including 7 different imaging modalities, were eligible for this NMA. In the pairwise meta-analysis, 18F-FDOPA PET/CT had a relatively high value of all the outcomes (sensitivity: 10.195 [5.332–19.493]; specificity: 17.906 [5.950–53.884]; NPV: 16.819 [7.033–40.218]; PPV: 11.154 [4.216–29.512]; and DR 5.616 [3.609–8.739]). In the NMA, 18F-FDOPA PET/CT exhibited relatively high sensitivity in all subgroups (all data: 0.94 [0.87–0.98]; primary tumor: 0.89 [0.53–1]; bone/bone marrow metastases: 0.96 [0.83–1]; and primary tumor and metastases (P + M): 0.92 [0.80–0.97]), the highest specificity in the subgroup of P + M (0.85 [0.61–0.97]), and achieved the highest superiority index in the subgroups of all data (8.57 [1–15]) and P + M (7.25 [1–13]). Conclusion 18F-FDOPA PET/CT exhibited the best diagnostic performance in the comprehensive detection of primary tumor and metastases for neuroblastic tumors, followed by 68Ga-somatostatin analogs, 123I-meta-iodobenzylguanidine (MIBG), 18F-FDG, and 131I-MIBG tomographic imaging.
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22
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Pezeshki PS, Moeinafshar A, Ghaemdoust F, Razi S, Keshavarz-Fathi M, Rezaei N. Advances in pharmacotherapy for neuroblastoma. Expert Opin Pharmacother 2021; 22:2383-2404. [PMID: 34254549 DOI: 10.1080/14656566.2021.1953470] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Neuroblastoma is the most prevalent cancer type diagnosed within the first year after birth and accounts for 15% of deaths from pediatric cancer. Despite the improvements in survival rates of patients with neuroblastoma, the incidence of the disease has increased over the last decade. Neuroblastoma tumor cells harbor a vast range of variable and heterogeneous histochemical and genetic alterations which calls for the need to administer individualized and targeted therapies to induce tumor regression in each patient. AREAS COVERED This paper provides reviews the recent clinical trials which used chemotherapeutic and/or targeted agents as either monotherapies or in combination to improve the response rate in patients with neuroblastoma, and especially high-risk neuroblastoma. It also reviews some of the prominent preclinical studies which can provide the rationale for future clinical trials. EXPERT OPINION Although some distinguished advances in pharmacotherapy have been made to improve the survival rate and reduce adverse events in patients with neuroblastoma, a more comprehensive understanding of the mechanisms of tumorigenesis, resistance to therapies or relapse, identifying biomarkers of response to each specific drug, and developing predictive preclinical models of the tumor can lead to further breakthroughs in the treatment of neuroblastoma.
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Affiliation(s)
- Parmida Sadat Pezeshki
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Aysan Moeinafshar
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Ghaemdoust
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Razi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Keshavarz-Fathi
- Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden
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68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy. Nucl Med Commun 2021; 41:1169-1177. [PMID: 32796449 DOI: 10.1097/mnm.0000000000001265] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.
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Ambrosini V, Kunikowska J, Baudin E, Bodei L, Bouvier C, Capdevila J, Cremonesi M, de Herder WW, Dromain C, Falconi M, Fani M, Fanti S, Hicks RJ, Kabasakal L, Kaltsas G, Lewington V, Minozzi S, Cinquini M, Öberg K, Oyen WJG, O'Toole D, Pavel M, Ruszniewski P, Scarpa A, Strosberg J, Sundin A, Taïeb D, Virgolini I, Wild D, Herrmann K, Yao J. Consensus on molecular imaging and theranostics in neuroendocrine neoplasms. Eur J Cancer 2021; 146:56-73. [PMID: 33588146 DOI: 10.1016/j.ejca.2021.01.008] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/31/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023]
Abstract
Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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Affiliation(s)
- Valentina Ambrosini
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Italy; Nuclear Medicine, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
| | - Jolanta Kunikowska
- Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland
| | - Eric Baudin
- Endocrine Oncolgy Unit, Institut Gustave Roussy, Villejuif Cedex, France
| | - Lisa Bodei
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Catherine Bouvier
- International Neuroendocrine Cancer Alliance (INCA), Leamington Spa, UK
| | - Jaume Capdevila
- Medical Oncology Department, Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Marta Cremonesi
- Radiation Research Unit, Istituto Europeo di Oncologia, IRCCS, Milano, Italy
| | - Wouter W de Herder
- Erasmus MC & Erasmus MC Cancer Center, ENETS Center of Excellence Rotterdam, Rotterdam, the Netherlands
| | | | - Massimo Falconi
- Pancreas Translational & Research Institute, Scientific Institute San Raffaele Hospital and University Vita-Salute, Milan, Italy
| | - Melpomeni Fani
- Division of Radiopharmaceutical Chemistry, University Hospital Basel, Basel, Switzerland
| | - Stefano Fanti
- IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Italy; Nuclear Medicine, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy
| | - Rodney J Hicks
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
| | - Levent Kabasakal
- Istanbul University-Cerrahpaşa, Faculty of Medicine, Department of Nuclear Medicine, Turkey
| | - Gregory Kaltsas
- National and Kapodistrian University of Athens, Athens, Greece
| | | | - Silvia Minozzi
- Laboratory of Clinical Research Methodology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Michela Cinquini
- Laboratory of Clinical Research Methodology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Kjell Öberg
- Dept of Endocrine Oncology, University Hospital Uppsala, Sweden
| | - Wim J G Oyen
- Humanitas University and Humanitas Clinical and Research Center, Milan, Italy; Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Radiology and Nuclear Medicine, Rijnstate Hospital Arnhem, the Netherlands
| | | | - Marianne Pavel
- Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Philippe Ruszniewski
- Department of Pancreatology, Beaujon Hospital, Université de Paris, Clichy, France
| | - Aldo Scarpa
- ARC-NET Centre for Applied Research on Cancer and Department of Pathology, University of Verona, Italy
| | | | - Anders Sundin
- Department of Surgical Sciences, Uppsala University, University Hospital, Sweden
| | - David Taïeb
- Department of Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France
| | - Irene Virgolini
- Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Damian Wild
- Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
| | - Ken Herrmann
- Department of Nuclear Medicine, Universitätsklinikum, Essen, Germany.
| | - James Yao
- Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Haddad T, Fard-Esfahani A, Vali R. A review of pediatric neuroendocrine tumors, their detection, and treatment by radioisotopes. Nucl Med Commun 2021; 42:21-31. [PMID: 33044400 DOI: 10.1097/mnm.0000000000001305] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Neuroendocrine tumors (NETs) are rare in childhood. Neuroblastoma is the most common pediatric extracranial solid tumor, occurring >90% in children younger than 5 years of age. Pheochromocytoma and paraganglioma are rare NETs, causing hypertension in 0.5-2% of hypertensive children. Gastroenteropancreatic NETs can occur in children and are classified into carcinoids and pancreatic tumors. Nuclear medicine procedures have an essential role both in the diagnosis and treatment of NETs. Metaiodobenzylguanidine (MIBG) labeled with radioiodine has a well-established role in diagnosis as well as therapeutic management of the neuroblastoma group of diseases. During recent decades, establishing the abundant expression of somatostatin receptors by NETs first led to scintigraphy with somatostatin analogs (i.e. Tc/In-octreotide) and, later, with the emergence of positron-emitting labeled agents (i.e. Ga-DOTATATE/DOTATOC/DOTANOC) PET scans with significantly higher detection efficiency became available. Therapy with somatostatin analogs labeled with beta emitters such as Lu-177 and Y-90, known as peptide receptor radionuclide therapy, is a promising new option in the management of patients with inoperable or metastasized NETs. In this article, pediatric NETs are briefly reviewed and the role of radioactive agents in the detection and treatment of these tumors is discussed.
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Affiliation(s)
- Tara Haddad
- Diagnostic Imaging Department, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
| | - Armaghan Fard-Esfahani
- Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Vali
- Diagnostic Imaging Department, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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Snyder SE, Butch ER, Shulkin BL. Radiopharmaceuticals in Pediatric Nuclear Medicine. HANDBOOK OF RADIOPHARMACEUTICALS 2020:653-701. [DOI: 10.1002/9781119500575.ch21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Jacobson AF, Matsuoka DT. Noradrenergic uptake in the liver on 123 I-mIBG imaging: Influence of heart failure and diabetes. J Gastroenterol Hepatol 2020; 35:2151-2157. [PMID: 32410288 DOI: 10.1111/jgh.15096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 04/15/2020] [Accepted: 05/02/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Imaging noradrenergic uptake in the liver with norepinephrine analog 123 I-meta-iodobenzylguanidine (mIBG) was explored in normal controls and patients with heart failure (HF). METHODS A total of 961 HF (343 with diabetes mellitus [DM]) and 94 control subjects underwent anterior planar mIBG images including upper abdomen at 15 min (early) and 3 h 50 min (late) post-injection. Decay-corrected liver activity normalized to injected activity and body surface area (counts/pixel [cpp]/MBq/m2 ) was compared in three groups: HF with DM; HF without DM; and controls. Associations with plasma norepinephrine, liver function tests, and level of cardiac innervation were explored. RESULTS In controls, liver mIBG activity decreased over time (early: 2.78 vs late: 2.43 cpp/MBq/m2 , P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85 vs 2.93 [P = 0.005]; HF with DM: 2.37 vs 2.43 [P = 0.054]). Early liver activity was lower in HF with DM subjects than in the other groups (P < 0.001); late liver activity was higher in HF without DM than in the other two groups (P < 0.01). Subjects with elevated plasma norepinephrine (> 520 pg/mL) or ≥ 1 abnormal liver function test had lower early and late liver activity. In subjects with preserved cardiac mIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. CONCLUSIONS In HF subjects, liver mIBG activity increased over time, reversing the normal washout pattern, suggesting a compensatory change in sympathetic nerve function. DM, abnormal liver function tests, and decreased cardiac innervation were associated with decreased liver mIBG uptake in HF.
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Stirrup J, Gregg S, Baavour R, Roth N, Breault C, Agostini D, Ernst S, Underwood SR. Hybrid solid-state SPECT/CT left atrial innervation imaging for identification of left atrial ganglionated plexi: Technique and validation in patients with atrial fibrillation. J Nucl Cardiol 2020; 27:1939-1950. [PMID: 30694425 DOI: 10.1007/s12350-018-01535-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/19/2018] [Indexed: 01/19/2023]
Abstract
BACKGROUND Ablating left atrial (LA) ganglionated plexi (GP), identified invasively by high-frequency stimulation (HFS) during pulmonary vein isolation (PVI), may reduce atrial fibrillation (AF) recurrence. 123I-metaiodobenzylguanidine (123I-mIBG) solid-state SPECT LA innervation imaging (LAII) has the spatial resolution to detect LAGP non-invasively but this has never been demonstrated in clinical practice. METHODS 20 prospective patients with paroxysmal AF scheduled for PVI underwent 123I-mIBG LAII. High-resolution tomograms, reconstructed where possible using cardiorespiratory gating, were co-registered with pre-PVI cardiac CT. Location and reader confidence (1 [low] to 3 [high]) in discrete 123I-mIBG LA uptake areas (DUAs) were recorded and correlated with HFS. RESULTS A total of 73 DUAs were identified, of which 59 (81%) were HFS positive (HFS +). HFS + likelihood increased with reader confidence (92% [score 3]). 64% of HFS-negative DUAs occurred over the lateral and inferior LA. Cardiorespiratory gating reduced the number of DUAs per patient (4 vs 7, P = .001) but improved: HFS + predictive value (76% vs 49%); reader confidence (2 vs 1, P = .02); and inter-observer, intra-observer, and inter-study agreement (κ = 0.84 vs 0.68; 0.82 vs 0.74; 0.64 vs 0.53 respectively). CONCLUSIONS 123I-mIBG SPECT/CT LAII accurately and reproducibly identifies GPs verified by HFS, particularly when reconstructed with cardiorespiratory gating.
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Affiliation(s)
- J Stirrup
- Department of Cardiology, Royal Berkshire Hospital NHS Foundation Trust, Craven Road, Reading, RG1 5AN, United Kingdom.
| | - S Gregg
- Department of Nuclear Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
| | - R Baavour
- Spectrum Dynamics Medical, Caesarea, Israel
| | - N Roth
- Spectrum Dynamics Medical, Caesarea, Israel
| | - C Breault
- Spectrum Dynamics Medical, Caesarea, Israel
| | - D Agostini
- Department of Nuclear Medicine, CHU Caen and Normandy University EA 4650, Caen, France
| | - S Ernst
- Department of Cardiology, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
- Cardiovascular Research Center, Royal Brompton and National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - S R Underwood
- Department of Nuclear Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
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Kotanidou EP, Giza S, Tsinopoulou VR, Vogiatzi M, Galli-Tsinopoulou A. Diagnosis and Management of Endocrine Hypertension in Children and Adolescents. Curr Pharm Des 2020; 26:5591-5608. [PMID: 33185153 DOI: 10.2174/1381612826666201113103614] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Hypertension in childhood and adolescence has increased in prevalence. Interest in the disease was raised after the 2017 clinical practice guidelines of the American Academy of Paediatrics on the definition and classification of paediatric hypertension. Among the secondary causes of paediatric hypertension, endocrine causes are relatively rare but important due to their unique treatment options. Excess of catecholamine, glucocorticoids and mineralocorticoids, congenital adrenal hyperplasia, hyperaldosteronism, hyperthyroidism and other rare syndromes with specific genetic defects are endocrine disorders leading to paediatric and adolescent hypertension. Adipose tissue is currently considered the major endocrine gland. Obesity-related hypertension constitutes a distinct clinical entity leading to an endocrine disorder. The dramatic increase in the rates of obesity during childhood has resulted in a rise in obesity-related hypertension among children, leading to increased cardiovascular risk and associated increased morbidity and mortality. This review presents an overview of pathophysiology and diagnosis of hypertension resulting from hormonal excess, as well as obesity-related hypertension during childhood and adolescence, with a special focus on management.
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Affiliation(s)
- Eleni P Kotanidou
- Second Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Styliani Giza
- Fourth Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece
| | - Vasiliki-Regina Tsinopoulou
- Second Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Maria Vogiatzi
- Division of Endocrinology and Diabetes, Children' s Hospital of Philadelphia, PA 19104, United States
| | - Assimina Galli-Tsinopoulou
- Second Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
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Zafar A, Wang W, Liu G, Wang X, Xian W, McKeon F, Foster J, Zhou J, Zhang R. Molecular targeting therapies for neuroblastoma: Progress and challenges. Med Res Rev 2020; 41:961-1021. [PMID: 33155698 PMCID: PMC7906923 DOI: 10.1002/med.21750] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/25/2020] [Accepted: 10/28/2020] [Indexed: 01/09/2023]
Abstract
There is an urgent need to identify novel therapies for childhood cancers. Neuroblastoma is the most common pediatric solid tumor, and accounts for ~15% of childhood cancer‐related mortality. Neuroblastomas exhibit genetic, morphological and clinical heterogeneity, which limits the efficacy of existing treatment modalities. Gaining detailed knowledge of the molecular signatures and genetic variations involved in the pathogenesis of neuroblastoma is necessary to develop safer and more effective treatments for this devastating disease. Recent studies with advanced high‐throughput “omics” techniques have revealed numerous genetic/genomic alterations and dysfunctional pathways that drive the onset, growth, progression, and resistance of neuroblastoma to therapy. A variety of molecular signatures are being evaluated to better understand the disease, with many of them being used as targets to develop new treatments for neuroblastoma patients. In this review, we have summarized the contemporary understanding of the molecular pathways and genetic aberrations, such as those in MYCN, BIRC5, PHOX2B, and LIN28B, involved in the pathogenesis of neuroblastoma, and provide a comprehensive overview of the molecular targeted therapies under preclinical and clinical investigations, particularly those targeting ALK signaling, MDM2, PI3K/Akt/mTOR and RAS‐MAPK pathways, as well as epigenetic regulators. We also give insights on the use of combination therapies involving novel agents that target various pathways. Further, we discuss the future directions that would help identify novel targets and therapeutics and improve the currently available therapies, enhancing the treatment outcomes and survival of patients with neuroblastoma.
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Affiliation(s)
- Atif Zafar
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA
| | - Wei Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.,Drug Discovery Institute, University of Houston, Houston, Texas, USA
| | - Gang Liu
- Department of Pharmacology and Toxicology, Chemical Biology Program, University of Texas Medical Branch, Galveston, Texas, USA
| | - Xinjie Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA
| | - Wa Xian
- Department of Biology and Biochemistry, Stem Cell Center, University of Houston, Houston, Texas, USA
| | - Frank McKeon
- Department of Biology and Biochemistry, Stem Cell Center, University of Houston, Houston, Texas, USA
| | - Jennifer Foster
- Department of Pediatrics, Texas Children's Hospital, Section of Hematology-Oncology Baylor College of Medicine, Houston, Texas, USA
| | - Jia Zhou
- Department of Pharmacology and Toxicology, Chemical Biology Program, University of Texas Medical Branch, Galveston, Texas, USA
| | - Ruiwen Zhang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.,Drug Discovery Institute, University of Houston, Houston, Texas, USA
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Pictorial review of the clinical applications of MIBG in neuroblastoma: current practices. Clin Transl Imaging 2020. [DOI: 10.1007/s40336-020-00392-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Davis L, Smith AL, Aldridge MD, Foulkes J, Peet C, Wan S, Gains JE, Bomanji JB, Gaze MN. Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics. J Pers Med 2020; 10:E174. [PMID: 33081161 PMCID: PMC7711590 DOI: 10.3390/jpm10040174] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/13/2020] [Accepted: 10/14/2020] [Indexed: 02/06/2023] Open
Abstract
Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death. A partner radiopharmaceutical, most commonly the same vector labelled with a different radioactive atom, with emissions suitable for gamma camera or positron emission tomography imaging, is used to select patients for treatment and to assess response. The use of these pairs of radio-labelled drugs, one optimised for therapy, the other for diagnostic purposes, is referred to as theragnostics. Theragnostics is increasingly moving away from a fixed number of defined activity administrations, to a much more individualised or personalised approach, with the aim of improving treatment outcomes, and minimising toxicity. There is, however, still significant scope for further progress in that direction. The main tools for personalisation are the following: imaging biomarkers for better patient selection; predictive and post-therapy dosimetry to maximise the radiation dose to the tumour while keeping organs at risk within tolerance limits; imaging for assessment of treatment response; individualised decision making and communication about radiation protection, adjustments for toxicity, inpatient and outpatient care.
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Affiliation(s)
- LauraMay Davis
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK; (L.D.); (A.-L.S.); (M.D.A.); (J.B.B.)
| | - April-Louise Smith
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK; (L.D.); (A.-L.S.); (M.D.A.); (J.B.B.)
| | - Matthew D. Aldridge
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK; (L.D.); (A.-L.S.); (M.D.A.); (J.B.B.)
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
| | - Jack Foulkes
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
| | - Connie Peet
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
| | - Simon Wan
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
| | - Jennifer E. Gains
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
| | - Jamshed B. Bomanji
- Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London NW1 2BU, UK; (L.D.); (A.-L.S.); (M.D.A.); (J.B.B.)
| | - Mark N. Gaze
- Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK; (J.F.); (C.P.); (S.W.); (J.E.G.)
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Diagnosis and treatment of a diaphragmatic pheochromocytoma: A case report. Int J Surg Case Rep 2020; 71:78-81. [PMID: 32446227 PMCID: PMC7242994 DOI: 10.1016/j.ijscr.2020.04.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 03/31/2020] [Accepted: 04/17/2020] [Indexed: 12/14/2022] Open
Abstract
Ectopic pheochromocytoma seldom occurs on the diaphragm and is hard to diagnose. Combination of catecholamine, CT and especially MIBG can assist in diagnosis of ectopic pheochromocytoma. Surgery may the first-choice treatment for ectopic pheochromocytomas. Background Ectopic pheochromocytomas, the incidence of which is >15%, can occur throughout the entire body but seldom on the diaphragm. Surgery may the first-choice treatment for ectopic pheochromocytomas. Presentation of case We herein describe a 61-year-old woman with an atopic diaphragmatic pheochromocytoma. She had a 7-year history of paroxysmal headaches, palpitations, and hypertension with no obvious causes; these symptoms were alleviated by nifedipine and metoprolol. Computed tomography (CT) revealed a slightly hypodense lesion on top of the right hepatic lobe. A Metaiodobenzylguanidine (MIBG) scan showed increased radioactive in the lesion. After adequate preoperative preparation, we removed the mass. During the operation, we found that the mass was located on the diaphragm. The pathological examination showed that the main pathologic change was paraganglioma. The patient recovered well after surgery with no recurrence of her hypertension, palpitation, or headache. Conclusions Diaphragmatic pheochromocytoma is a rare kind of ectopic pheochromocytomas, which can also affect the patient’s quality of life. Combination of qualitative and positioning tests can assist in diagnosis of ectopic pheochromocytoma. Surgical resection is an effective treatment method.
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[TWO CASES OF FALSE POSITIVE 123I-MIBG SCINTIGRAPHY FINDINGS OF UPTAKE IN ADRENAL TUMORS]. Nihon Hinyokika Gakkai Zasshi 2020; 111:159-163. [PMID: 34670917 DOI: 10.5980/jpnjurol.111.159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Case 1 was a 71-year-old female who had been examined by her primary care physician for palpitation and hypertension. Urinary hormone test results revealed elevated urine metanephrine at 0.20 mg/day, urine normetanephrine at 0.45 mg/day and urine noradrenalin at 234.9 μg/day. 123I-MIBG scintigraphy showed uptake in the right suprarenal area, thus she was referred to our department because of pheochromocytoma. She underwent a laparoscopic right adrenalectomy and pathological results led to a diagnosis of adrenocortical adenoma. Case 2 was a 70-year-old female who had been examined at our hospital for hypertension. Blood hormone test results revealed elevated noradrenalin at 0.70 ng/ml. 123I-MIBG scintigraphy showed uptake in the left suprarenal area and she was referred to our department because of pheochromocytoma. She underwent a laparoscopic left adrenalectomy, thus pathological results showed no tumor lesion.
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Abstract
Neuroblastoma is a heterogenous disease, with solid tumors arising in the adrenal gland or paraspinal regions in young children. Neuroblastoma is unique, with varied presentation and prognosis based on primary location and tumor stage. Tumor behavior and response to treatment ranges from spontaneous regression to disseminated, lethal disease depending on the individual biology of a patient's tumor. Stratification of the disease has changed, with patients now placed in low, intermediate, and high-risk categories depending on age, stage, and tumor biology. Long-term survival for the high-risk subset of patients with metastatic disease is <40% despite aggressive multimodal therapy. Derived from sympathoadrenal cells of the adrenal medulla and sympathetic nervous system, both malignant neuroblastoma and differentiated tumors have specialized norepinephrine transporter (NET) receptors which are naturally occurring in the sympathetic nervous system throughout the body. Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that undergoes active uptake by NET receptors resulting in accumulation in neuroblastoma as well as tissues normally expressing the NET receptor. When radioiodine labeled, MIBG can be used for both diagnosis and treatment. This article describes the history of MIBG use in neuroblastoma, including its utility as an imaging modality for diagnosis as well as the varied ways in which is it included in the multimodal treatment algorithm.
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Bergman MJ, Prasad NR, Brumfiel CM, Harley EH. Neonatal neuroblastoma in otolaryngology: A case and literature review. INT J PEDIAT OTO CAS 2019. [DOI: 10.1016/j.pedeo.2019.100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Abstract
Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.
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Theerakulpisut D, Raruenrom Y, Wongsurawat N, Somboonporn C. Value of SPECT/CT in Diagnostic I-131 MIBG Scintigraphy in Patients with Neuroblastoma. Nucl Med Mol Imaging 2018; 52:350-358. [PMID: 30344783 DOI: 10.1007/s13139-018-0532-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/12/2018] [Accepted: 06/28/2018] [Indexed: 12/27/2022] Open
Abstract
Purpose Diagnostic I-131 MIBG scintigraphy is an important imaging modality for evaluation of patients with neuroblastoma (NB) especially in centers where I-123 MIBG is not available. Single photon emission computed tomography/computed tomography (SPECT/CT) could potentially improve lesion detection over planar scintigraphy, but studies regarding its usefulness as an add-on to diagnostic I-131 MIBG scintigraphy are limited. This study aimed to determine the usefulness and factors related to usefulness of SPECT/CT in diagnostic I-131 MIBG scintigraphy in NB patients. Methods Usefulness of SPECT/CT for lesion detection, lesion localization, resolving suspicious findings, and clarifying the nature of lesions on anatomical imaging were retrospectively reviewed in 86 diagnostic planar I-131 MIBG scintigrams with add-on SPECT/CT. Results SPECT/CT detected additional lesions in 23.2%(20/86), helped localize lesions in 21.1%(8/38), resolved suspicious findings in 85.7%(6/7), determined functional status of lesions on anatomical imaging in 94.4%(17/18), and changed diagnosis from a negative to a positive study in 19.5%(8/41). Independent predictors of SPECT/CT being useful included presence of suspicious findings on planar imaging (OR 99.08; 95% C.I. 6.99-1404.41; p = 0.001), positive findings on planar imaging (OR 4.61; 95% C.I. 1.05, 20.28; p < 0.001), and presence of structural lesions on anatomical imaging (OR 32.54; 95% C.I. 5.37-196.96; p < 0.001). Conclusion SPECT/CT is a useful add-on to diagnostic planar I-131 MIBG scintigraphy. Predictors of usefulness of SPECT/CT include suspicious or positive findings on planar scintigraphy and the presence of structural lesions on anatomical imaging.
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Affiliation(s)
- Daris Theerakulpisut
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Khon Kaen University, 123 Mittraparp highway, Muang, Khon Kaen, 40002 Thailand
| | - Yutapong Raruenrom
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Khon Kaen University, 123 Mittraparp highway, Muang, Khon Kaen, 40002 Thailand
| | - Nantaporn Wongsurawat
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Khon Kaen University, 123 Mittraparp highway, Muang, Khon Kaen, 40002 Thailand
| | - Charoonsak Somboonporn
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Khon Kaen University, 123 Mittraparp highway, Muang, Khon Kaen, 40002 Thailand
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Inoue M, Okamura K, Kitaoka C, Kinoshita F, Namitome R, Nakamura U, Shiota M, Goto K, Ohtsubo T, Matsumura K, Oda Y, Eto M, Kitazono T. Metyrapone-responsive ectopic ACTH-secreting pheochromocytoma with a vicious cycle via a glucocorticoid-driven positive-feedback mechanism. Endocr J 2018; 65:755-767. [PMID: 29760304 DOI: 10.1507/endocrj.ej18-0025] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
In ectopic ACTH-secreting pheochromocytoma, combined ACTH-driven hypercortisolemia and hypercatecholaminemia are serious conditions, which can be fatal if not diagnosed and managed appropriately, especially when glucocorticoid-driven positive feedback is suggested with a high ACTH/cortisol ratio. A 46-year-old man presented with headache, rapid weight loss, hyperhidrosis, severe hypertension and hyperglycemia without typical Cushingoid appearance. Endocrinological examinations demonstrated elevated plasma and urine catecholamines, serum cortisol and plasma ACTH. Moreover, his ACTH/cortisol ratio and catecholamine levels were extremely high, suggesting catecholamine-dominant ACTH-secreting pheochromocytoma. Computed tomography revealed a large right adrenal tumor. 18F-FDG positron emission tomography showed uptake in the area of the adrenal tumor, while 123I-metaiodobenzylguanidine scintigraphy showed no accumulation. His plasma ACTH level paradoxically became elevated after a dexamethasone suppression test. After metyrapone administration, not only serum cortisol but also plasma ACTH levels were exponentially decreased almost in parallel, suggesting a glucocorticoid-driven positive-feedback regulation in this rapidly exacerbated ectopic ACTH-producing pheochromocytoma. Interestingly enough, plasma catecholamine levels were also decreased by metyrapone, although they remained extremely high. He became severely dehydrated due to hypoadrenalism requiring hydrocortisone supplementation. His clinical signs and symptoms were improved, and right adrenalectomy was performed uneventfully, resulting in complete remission of pheochromocytoma and Cushing's syndrome. A glucocorticoid-driven positive-feedback regulation in this ectopic ACTH-secreting pheochromocytoma created a vicious cycle with rapid exacerbation of both hypercortisolemia and hypercatecholaminemia with extremely elevated plasma ACTH level. Metyrapone was clinically effective to stop this vicious cycle; nonetheless, great care must be taken to avoid hypoadrenalism especially when hypercatecholaminemia remained.
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Affiliation(s)
- Minako Inoue
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ken Okamura
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Chie Kitaoka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Fumio Kinoshita
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ryo Namitome
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Udai Nakamura
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masaki Shiota
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichi Goto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshio Ohtsubo
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kiyoshi Matsumura
- Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masatoshi Eto
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Han S, Suh CH, Woo S, Kim YJ, Lee JJ. Performance of 68Ga-DOTA–Conjugated Somatostatin Receptor–Targeting Peptide PET in Detection of Pheochromocytoma and Paraganglioma: A Systematic Review and Metaanalysis. J Nucl Med 2018; 60:369-376. [DOI: 10.2967/jnumed.118.211706] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 07/09/2018] [Indexed: 01/28/2023] Open
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Vatsadze SZ, Eremina OE, Veselova IA, Kalmykov SN, Nenajdenko VG. 18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects. RUSSIAN CHEMICAL REVIEWS 2018. [DOI: 10.1070/rcr4752] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, Feldmann G, Ahmadzadehfar H, Essler M. Theranostics in nuclear medicine practice. Onco Targets Ther 2017; 10:4821-4828. [PMID: 29042793 PMCID: PMC5633297 DOI: 10.2147/ott.s140671] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.
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Affiliation(s)
- Anna Yordanova
- Department of Nuclear Medicine (Clinical Nuclear Medicine)
| | | | | | | | | | | | - Georg Feldmann
- Department of Medicine 3, University Hospital Bonn, Bonn, Germany
| | | | - Markus Essler
- Department of Nuclear Medicine (Clinical Nuclear Medicine)
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Pandit-Taskar N, Modak S. Norepinephrine Transporter as a Target for Imaging and Therapy. J Nucl Med 2017; 58:39S-53S. [PMID: 28864611 DOI: 10.2967/jnumed.116.186833] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Accepted: 07/19/2017] [Indexed: 01/01/2023] Open
Abstract
The norepinephrine transporter (NET) is essential for norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. In neuroendocrine tumors, NET can be targeted for imaging as well as therapy. One of the most widely used theranostic agents targeting NET is metaiodobenzylguanidine (MIBG), a guanethidine analog of norepinephrine. 123I/131I-MIBG theranostics have been applied in the clinical evaluation and management of neuroendocrine tumors, especially in neuroblastoma, paraganglioma, and pheochromocytoma. 123I-MIBG imaging is a mainstay in the evaluation of neuroblastoma, and 131I-MIBG has been used for the treatment of relapsed high-risk neuroblastoma for several years, however, the outcome remains suboptimal. 131I-MIBG has essentially been only palliative in paraganglioma/pheochromocytoma patients. Various techniques of improving therapeutic outcomes, such as dosimetric estimations, high-dose therapies, multiple fractionated administration and combination therapy with radiation sensitizers, chemotherapy, and other radionuclide therapies, are being evaluated. PET tracers targeting NET appear promising and may be more convenient options for the imaging and assessment after treatment. Here, we present an overview of NET as a target for theranostics; review its current role in some neuroendocrine tumors, such as neuroblastoma, paraganglioma/pheochromocytoma, and carcinoids; and discuss approaches to improving targeting and theranostic outcomes.
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Affiliation(s)
| | - Shakeel Modak
- Memorial Sloan Kettering Cancer Center, New York, New York
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Yang J, Shen J, Fuller PJ. Diagnosing endocrine hypertension: a practical approach. Nephrology (Carlton) 2017; 22:663-677. [PMID: 28556585 DOI: 10.1111/nep.13078] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 05/10/2017] [Accepted: 05/24/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Jun Yang
- Centre for Endocrinology and Metabolism; Hudson Institute of Medical Research; Melbourne Victoria Australia
- Department of Endocrinology; Monash Health; Melbourne Victoria Australia
| | - Jimmy Shen
- Centre for Endocrinology and Metabolism; Hudson Institute of Medical Research; Melbourne Victoria Australia
- Department of Endocrinology; Monash Health; Melbourne Victoria Australia
| | - Peter J. Fuller
- Centre for Endocrinology and Metabolism; Hudson Institute of Medical Research; Melbourne Victoria Australia
- Department of Endocrinology; Monash Health; Melbourne Victoria Australia
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Spencer-Bonilla G, Singh Ospina N, Rodriguez-Gutierrez R, Brito JP, Iñiguez-Ariza N, Tamhane S, Erwin PJ, Murad MH, Montori VM. Systematic reviews of diagnostic tests in endocrinology: an audit of methods, reporting, and performance. Endocrine 2017; 57:18-34. [PMID: 28585154 DOI: 10.1007/s12020-017-1298-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 04/01/2017] [Indexed: 01/25/2023]
Abstract
BACKGROUND Systematic reviews provide clinicians and policymakers estimates of diagnostic test accuracy and their usefulness in clinical practice. We identified all available systematic reviews of diagnosis in endocrinology, summarized the diagnostic accuracy of the tests included, and assessed the credibility and clinical usefulness of the methods and reporting. METHODS We searched Ovid MEDLINE, EMBASE, and Cochrane CENTRAL from inception to December 2015 for systematic reviews and meta-analyses reporting accuracy measures of diagnostic tests in endocrinology. Experienced reviewers independently screened for eligible studies and collected data. We summarized the results, methods, and reporting of the reviews. We performed subgroup analyses to categorize diagnostic tests as most useful based on their accuracy. RESULTS We identified 84 systematic reviews; half of the tests included were classified as helpful when positive, one-fourth as helpful when negative. Most authors adequately reported how studies were identified and selected and how their trustworthiness (risk of bias) was judged. Only one in three reviews, however, reported an overall judgment about trustworthiness and one in five reported using adequate meta-analytic methods. One in four reported contacting authors for further information and about half included only patients with diagnostic uncertainty. CONCLUSION Up to half of the diagnostic endocrine tests in which the likelihood ratio was calculated or provided are likely to be helpful in practice when positive as are one-quarter when negative. Most diagnostic systematic reviews in endocrine lack methodological rigor, protection against bias, and offer limited credibility. Substantial efforts, therefore, seem necessary to improve the quality of diagnostic systematic reviews in endocrinology.
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Affiliation(s)
- Gabriela Spencer-Bonilla
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA
| | - Naykky Singh Ospina
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Rene Rodriguez-Gutierrez
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Endocrinology, Department of Internal Medicine, University Hospital "Dr. Jose E. Gonzalez", Autonomous University of Nuevo Leon, Monterrey, MX, USA
| | - Juan P Brito
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
| | - Nicole Iñiguez-Ariza
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
| | - Shrikant Tamhane
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
| | | | - M Hassan Murad
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Preventive, Occupational, and Aerospace Medicine, Mayo Clinic, Rochester, MN, USA
| | - Victor M Montori
- Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA.
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA.
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Dimitriadis GK, Angelousi A, Weickert MO, Randeva HS, Kaltsas G, Grossman A. Paraneoplastic endocrine syndromes. Endocr Relat Cancer 2017; 24:R173-R190. [PMID: 28341725 DOI: 10.1530/erc-17-0036] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 03/24/2017] [Indexed: 12/13/2022]
Abstract
The majority of neoplasms are responsible for symptoms caused by mass effects to surrounding tissues and/or through the development of metastases. However, occasionally neoplasms, with or without endocrine differentiation, acquire the ability to secrete a variety of bioactive substances or induce immune cross-reactivity with the normal tissues that can lead to the development of characteristic clinical syndromes. These syndromes are named endocrine paraneoplastic syndromes when the specific secretory components (hormones, peptides or cytokines) are unrelated to the anticipated tissue or organ of origin. Endocrine paraneoplastic syndromes can complicate the patient's clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. These syndromes can precede, occur concomitantly or present at a later stage of tumour development, and along with the secreted substances constitute the biological 'fingerprint' of the tumour. Their detection can facilitate early diagnosis of the underlying neoplasia, monitor response to treatment and/or detect early recurrences following successful initial management. Although when associated with tumours of low malignant potential they usually do not affect long-term outcome, in cases of highly malignant tumours, endocrine paraneoplastic syndromes are usually associated with poorer survival outcomes. Recent medical advances have not only improved our understanding of paraneoplastic syndrome pathogenesis in general but also enhanced their diagnosis and treatment. Yet, given the rarity of endocrine paraneoplastic syndromes, there is a paucity of prospective clinical trials to guide management. The development of well-designed prospective multicentre trials remains a priority in the field in order to fully characterise these syndromes and provide evidence-based diagnostic and therapeutic protocols.
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Affiliation(s)
- Georgios K Dimitriadis
- The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Anna Angelousi
- Division of PathophysiologyNational and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Martin O Weickert
- The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Harpal S Randeva
- The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Gregory Kaltsas
- The Arden NET CoEWarwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
- Division of PathophysiologyNational and Kapodistrian University of Athens Medical School, Athens, Greece
- Oxford Centre for DiabetesEndocrinology and Metabolism, University of Oxford, Oxford, UK
| | - Ashley Grossman
- Oxford Centre for DiabetesEndocrinology and Metabolism, University of Oxford, Oxford, UK
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Abstract
Nuclear medicine has an important role in the management of many cancers in pediatric age group with multiple imaging modalities and radiopharmaceuticals targeting various biological uptake mechanisms. 18-Flourodeoxyglucose is the radiotracer of choice especially in patients with sarcoma and lymphoma. (18)FDG-PET, for sarcoma and lymphomas, is proved to be superior to conventional imaging in staging and therapy response. Although studies are limited in pediatric population, (18)FDG-PET/CT has found its way through international guidelines. Limitations and strengths of PET imaging must be noticed before adapting PET imaging in clinical protocols. Established new response criteria using multiple parameters derived from (18)FDG-PET would increase the accuracy and repeatability of response evaluation. Current data suggest that I-123 metaiodobenzylguanidine (MIBG) remains the tracer of choice in the evaluation of neuroblastoma (NB) because of its high sensitivity, specificity, diagnostic accuracy, and prognostic value. It is valuable in determining the response to therapy, surveillance for disease recurrence, and in selecting patients for I-131 therapy. SPECT/CT improves the diagnostic accuracy and the interpretation confidence of MIBG scans. (18)FDG-PET/CT is an important complementary to MIBG imaging despite its lack of specificity to NB. It is valuable in cases of negative or inconclusive MIBG scans and when MIBG findings underestimate the disease status as determined from clinical and radiological findings. F-18 DOPA is promising tracer that reflects catecholamine metabolism and is both sensitive and specific. F-18 DOPA scintigraphy provides the advantages of PET/CT imaging with early and short imaging times, high spatial resolution, inherent morphologic correlation with CT, and quantitation. Regulatory and production issues currently limit the tracer's availability. PET/CT with Ga-68 DOTA appears to be useful in NB imaging and may have a unique role in selecting patients for peptide receptor radionuclide therapy with somatostatin analogues. C-11 hydroxyephedrine PET/CT is a specific PET tracer for NB, but the C-11 label that requires an on-site cyclotron production and the high physiologic uptake in the liver and kidneys limit its use. I-124 MIBG is useful for I-131 MIBG pretherapeutic dosimetry planning. Its use for diagnostic imaging as well as the use of F-18 labeled MIBG analogues is currently experimental. PET/MR imaging is emerging and is likely to become an important tool in the evaluation. It provides metabolic and superior morphological data in one imaging session, expediting the diagnosis and lowering the radiation exposure. Radioactive iodines not only detect residual tissue and metastatic disease but also are used in the treatment of differentiated thyroid cancer. However, these are not well documented in pediatric age group like adult patients. Use of radioactivity in pediatric population is very important and strictly controlled because of the possibility of secondary malignities; therefore, management of oncological cases requires detailed literature knowledge. This article aims to review the literature on the use of radionuclide imaging and therapy in pediatric population with thyroid cancer, sarcomas, lymphoma, and NB.
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Affiliation(s)
- Pınar Özgen Kiratli
- Department of Nuclear Medicine, Hacettepe University Medical Center, Ankara, Turkey.
| | - Murat Tuncel
- Department of Nuclear Medicine, Hacettepe University Medical Center, Ankara, Turkey
| | - Zvi Bar-Sever
- Department of Nuclear Medicine, Schneider Children's Medical Center, Petah Tikva, Israel
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Bhanthumkomol P, Hijioka S, Mizuno N, Kuwahara T, Okuno N, Ito A, Tanaka T, Ishihara M, Hirayama Y, Onishi S, Niwa Y, Tajika M, Ito Y, Sasaki E, Inaba Y, Shimizu Y, Yatabe Y, Hara K. Uptake of 123I-metaiodobenzylguanidine by gastrointestinal stromal tumor. Clin J Gastroenterol 2017; 10:364-370. [DOI: 10.1007/s12328-017-0743-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Accepted: 04/18/2017] [Indexed: 10/19/2022]
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Wong K, Chondrogiannis S, Fuster D, Ruiz C, Marzola M, Giammarile F, Colletti P, Rubello D. Additional value of hybrid SPECT/CT systems in neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. Rev Esp Med Nucl Imagen Mol 2017. [DOI: 10.1016/j.remnie.2016.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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50
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Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2017:749-775. [DOI: 10.1007/978-3-319-26236-9_17] [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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