David Taïeb1, Abhishek Jha2, Carole Guerin3, Ying Pang2, Karen T Adams2, Clara C Chen4, Pauline Romanet5, Philippe Roche6, Wassim Essamet7, Alexander Ling8, Martha M Quezado9, Frédéric Castinetti10, Fréderic Sebag3, Karel Pacak2. 1. Department of Nuclear Medicine, La Timone University Hospital, Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille University, Marseille, France. 2. Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. 3. Department of Endocrine Surgery, Conception University Hospital, Aix-Marseille University, Marseille, France. 4. Nuclear Medicine Division, Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. 5. Laboratory of Molecular Biology, Conception Hospital and National Center for Scientific Research, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, Unité Mixte de Recherche 7286, Aix-Marseille University, Marseille, France. 6. Integrative Structural and Chemical Biology and INT-3D Molecular Modeling Platform, Cancer Research Centre of Marseille, National Center for Scientific Research, Unité Mixte de Recherche 7258, Marseille, France. 7. Department of Neuropathology, La Timone University Hospital, Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille University, Marseille, France. 8. Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. 9. Labaratory of Pathology, Center for Cancer Research, National Cancer Institute, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. 10. Department of Endocrinology, Conception University Hospital, Aix-Marseille University, Marseille, France.
Abstract
Context: MYC-associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of ~40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. Objective, Patients, and Design: The objective of the present study was to present our experience with contrast-enhanced computed tomography (CT) and 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET)/CT in six consecutive patients (four at the initial diagnosis and two at the follow-up evaluation) with rare, but clinically important, MAX-related PHEOs. In five patients, 18F-FDOPA was also compared with other radiopharmaceutical agents. Results: The patients had five different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilaterally and detected more adrenal and extra-adrenal lesions than did CT (per-lesion sensitivity, 90.9% vs 52.4% for CT/magnetic resonance imaging). The two PHEOs missed on 18F-FDOPA PET/CT were <1 cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTA,Tyr3-octreotate PET/CT detected fewer lesions than did 18F-FDOPA PET/CT in one of three patients, and 18F-fluorodeoxyglucose PET/CT was only faintly positive in two of four patients with underestimation of extra-adrenal lesions in one patient. Conclusions: MAX-related PHEOs exhibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEOs associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluations for these patients.
Context:MYC-associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of ~40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. Objective, Patients, and Design: The objective of the present study was to present our experience with contrast-enhanced computed tomography (CT) and 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET)/CT in six consecutive patients (four at the initial diagnosis and two at the follow-up evaluation) with rare, but clinically important, MAX-related PHEOs. In five patients, 18F-FDOPA was also compared with other radiopharmaceutical agents. Results: The patients had five different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilaterally and detected more adrenal and extra-adrenal lesions than did CT (per-lesion sensitivity, 90.9% vs 52.4% for CT/magnetic resonance imaging). The two PHEOs missed on 18F-FDOPA PET/CT were <1 cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTA,Tyr3-octreotate PET/CT detected fewer lesions than did 18F-FDOPA PET/CT in one of three patients, and 18F-fluorodeoxyglucose PET/CT was only faintly positive in two of four patients with underestimation of extra-adrenal lesions in one patient. Conclusions: MAX-related PHEOs exhibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEOs associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluations for these patients.
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