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Clin Endocrinol (Oxf). 2019 Sep 3. doi: 10.1111/cen.14086. [Epub ahead of print]

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

Author information

1
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, France.
2
Department of Head and Neck Surgery, Conception Hospital, Aix-Marseille Univ, France.
3
Department of Endocrinology, Conception University Hospital, Aix-Marseille University, France.
4
Department of Endocrine Surgery, Conception University Hospital, Aix-Marseille University, France.
5
Laboratory of Molecular Biology, Conception Hospital & CNRS, CRN2M UMR 7286, Aix-Marseille University, France.
6
Department of Public Health, EA3279 Self-perceived Health Assessment Research Unit, Aix-Marseille University, France.
7
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA.

Abstract

OBJECTIVES:

Nuclear imaging findings by virtue of phenotyping disease heavily depend on genetic background, metabolites, cell membrane specific targets, and signaling 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.

METHOD:

A cohort of 86 head and neck PPGL patients (including 3 metastatic) with normal metanephrines underwent 18 F-FDOPA PET/CT. The relationships between 18 F-FDOPA uptake and tumor genotype were evaluated.

RESULTS:

In non-metastatic HNPGL (50 non-SDHx/33 SDHx), no significant difference was observed between these 2 groups for SUVmax (p=0.256), SUVmean (p=0.188), MTV 42% (p=0.596) and total lesion uptake (p=0.144). Metastatic HNPGL also had high elevated uptake values.

CONCLUSIONS:

Our results suggest that SDH deficiency or metastatic behavior 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. This article is protected by copyright. All rights reserved.

KEYWORDS:

18F-FDOPA; genetics; paragangliomas; radionuclide imaging; succinate dehydrogenase

PMID:
31479526
DOI:
10.1111/cen.14086

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