Correlation of the Genotype of Paragangliomas and Pheochromocytomas with Their Metabolic Phenotype on 3,4-Dihydroxy-6-18F-Fluoro-l-Phenylalanin PET

Abstract

Paragangliomas and pheochromocytomas are genetically heterogeneous diseases. The purpose of this study was to determine the sensitivity and specificity of PET with 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanin ((18)F-DOPA) for the detection and staging of pheochromocytomas/paragangliomas. Furthermore, we assessed whether the genotypes of pheochromocytomas and paragangliomas correlate with the uptake of (18)F-DOPA. We retrospectively analyzed 101 consecutive patients who underwent (18)F-DOPA PET or (18)F-DOPA PET/CT for known or suspected pheochromocytomas or paragangliomas. Maximum (18)F-DOPA tumor uptake was quantified relative to uptake in the liver. Histopathology, cross-sectional imaging, and follow-up indicated the presence of paragangliomas and pheochromocytomas in 68 patients and the absence of a tumor in 33 patients. The average (18)F-DOPA uptake by paragangliomas and pheochromocytomas, expressed as a tumor-to-liver ratio, was 5.9 ± 5.2. There was no significant difference in uptake among patients with von Hippel Lindau syndrome (VHL; n = 19), succinate dehydrogenase B-D mutation (n = 21), neurofibromatosis type 1 (n = 1), RET (n = 1), no germline mutation (n = 20), or unknown mutation status (n = 6) (P = 0.84). All 8 patients with an SDHD mutation were true-positive on (18)F-DOPA PET. There were 2 cases of false-negative results each in the group with SDHB (2/12) and VHL mutations (2/19) and 1 false-negative result in the subgroup of patients with unknown mutation status (1/6). Overall, (18)F-DOPA PET yielded a sensitivity of 93% and a specificity of 88% for the detection of paragangliomas and pheochromocytomas on a patient basis (positive and negative predictive value, 94% and 85%, respectively). (18)F-DOPA PET is a sensitive and specific imaging modality for the detection and staging of pheochromocytomas and paragangliomas in different genotypes, including VHL-, SDHB-, and SDHD-mutation carriers, and in patients with no germline mutation.