Reichert Thibaut, Fakhry Nicolas, Lavieille Jean-Pierre, Amodru Vincent, Sebag Frédéric, Romanet Pauline, Loundou Anderson, Castinetti Frédéric, Pacak Karel, Montava Marion, Taïeb David
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.
Department of Head and Neck Surgery, Conception Hospital, Aix-Marseille Univ, Marseille, France.
Clin Endocrinol (Oxf). 2019 Dec;91(6):879-884. doi: 10.1111/cen.14086. Epub 2019 Oct 1.
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.
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.
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.
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.
基于疾病表型的核成像结果在很大程度上取决于遗传背景、代谢物、细胞膜特异性靶点和信号通路。与琥珀酸脱氢酶亚基突变（SDHx突变）相关的嗜铬细胞瘤（PPGL）比其他亚组的分化程度更低，因此可能缺乏摄取儿茶酚胺生物合成前体F-FDOPA的能力。然而，这种F-FDOPA阴性表型大多在交感神经起源的SDHx-PPGL中被报道，这表明基因型状态和位置（交感神经节与副交感神经节；肾上腺与肾上腺外）都可能影响F-FDOPA的摄取。本研究的目的是测试在肾上腺素/去甲肾上腺素浓度正常的情况下，SDHx是否会驱动F-FDOPA的摄取。
回顾性研究
一组86例头颈部PPGL患者（包括3例转移性患者），其甲氧基肾上腺素水平正常，接受了F-FDOPA PET/CT检查。评估了F-FDOPA摄取与肿瘤基因型之间的关系。
在非转移性头颈部嗜铬细胞瘤（50例非SDHx/33例SDHx）中，这两组在最大标准摄取值（SUVmax）（P = 0.256）、平均标准摄取值（SUVmean）（P = 0.188）、代谢体积（MTV）42%（P = 0.596）和总病灶摄取量（P = 0.144）方面未观察到显著差异。转移性头颈部嗜铬细胞瘤的摄取值也显著升高。
我们的结果表明，SDH缺陷或转移行为对头颈部嗜铬细胞瘤中F-FDOPA的摄取没有影响，这可能是由于它们的高分化状态，即使在转移阶段也是如此。F-FDOPA摄取的潜在预后价值需要在交感神经起源的转移性PPGL背景下进一步探索。
