6-18F-Fluoro-L-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to 123I-Metaiodobenzyl-Guanidine Scintigraphy in the Detection of Extraadrenal and Hereditary Pheochromocytomas and Paragangliomas: with Vesicular Monoamine Transporter Expression

Context: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by F-18-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than I-123-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. Objective: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. Design and Setting: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. Patients: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex, subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein, two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive adrenal incidentalomas. Main Outcome Measures: In all patients computed tomography scan and/or magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed. Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine transporter (VMAT)-1 and -2 and other markers. Results: A total of 64 lesions were found with both functional imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1 expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause. Conclusion: FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-scintigraphy. (J Clin Endocrinol Metab 95: 2800-2810, 2010)