Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: A F-FDOPA PET/CT study in head and neck paragangliomas.

Objectives: Nuclear imaging findings by virtue of phenotyping disease heavily depend on genetic background, metabolites, cell membrane specific targets and signalling pathways. PPGL related to succinate dehydrogenase subunits mutations (SDHx mutations) are less differentiated than other subgroups and therefore may lack to concentrate F-FDOPA, a precursor of catecholamines biosynthesis. However, this F-FDOPA negative phenotype has been reported mostly in SDHx-PPGL of sympathetic origin, suggesting that both genotype status and location (from sympathetic vs parasympathetic paraganglia; adrenal vs extra-adrenal) could influence F-FDOPA uptake. The aim of this study was to test if SDHx drives F-FDOPA uptake in presence of normal epinephrine/norepinephrine concentrations.

Design: Retrospective study PATIENTS: A cohort of 86 head and neck PPGL patients (including three metastatic) with normal metanephrines underwent F-FDOPA PET/CT. The relationships between F-FDOPA uptake and tumour genotype were evaluated.

Results: In nonmetastatic HNPGL (50 non-SDHx/33 SDHx), no significant difference was observed between these two groups for SUVmax (P = .256), SUVmean (P = .188), MTV 42% (P = .596) and total lesion uptake (P = .144). Metastatic HNPGL also had high elevated uptake values.

Conclusions: Our results suggest that SDH deficiency or metastatic behaviour have no influence on F-FDOPA uptake in HNPGL probably due to their very-well differentiation status, even at metastatic stage. The potential prognosticator value of F-FDOPA uptake would need to be further explored in the setting of metastatic PPGL of sympathetic origin.