Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: A 18 F-FDOPA PET/CT study in head and neck paragangliomas.

Abstract

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 18 F-FDOPA, a precursor of catecholamines biosynthesis. However, this 18 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 18 F-FDOPA uptake. The aim of this study was to test if SDHx drives 18 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 18 F-FDOPA PET/CT. The relationships between 18 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 18 F-FDOPA uptake in HNPGL probably due to their very-well differentiation status, even at metastatic stage. The potential prognosticator value of 18 F-FDOPA uptake would need to be further explored in the setting of metastatic PPGL of sympathetic origin.

• Authors: Thibaut Reichert, Nicolas Fakhry, Jean-Pierre Lavieille, Vincent Amodru, Frédéric Sebag, Pauline Romanet, Anderson Loundou, Frédéric Castinetti, Karel Pacak, Marion Montava, David Taïeb
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 91 Issue 6 Pg. 879-884 (12 2019) ISSN: 1365-2265 [Electronic] England
• PMID: 31479526 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• Succinate Dehydrogenase

Topics

• Adult
• Female
• Genotype
• Head and Neck Neoplasms (diagnostic imaging, enzymology)
• Humans
• Male
• Middle Aged
• Mutation
• Paraganglioma (diagnostic imaging, enzymology)
• Positron Emission Tomography Computed Tomography (methods)
• Radionuclide Imaging
• Retrospective Studies
• Succinate Dehydrogenase (deficiency, metabolism)