Genotype-dependent [¹⁸F]FDOPA uptake: quantitative evidence from a genetically stratified PPGL cohort.

Abstract

[¹⁸F]FDOPA PET/CT is widely used in the diagnostic work-up of pheochromocytoma and paraganglioma (PPGL), with the latter entity classified into genetic clusters 1a, 1b, and 2 and sporadic tumours, reflecting varying aggressiveness. We aimed to assess diagnostic performance and quantitative [¹⁸F]FDOPA uptake across genetic clusters. Consecutive PPGL patients with [¹⁸F]FDOPA PET/CT at initial diagnosis and available information on germline and/or somatic testing were included. Patients were grouped into genetic clusters. PET quantification included metabolic tumour volume (MTV) and maximum SUV(SUV_max), mean SUV(SUV_mean) and tumour-to-background ratio (TBR, SUV_max/liver SUV_mean). The diameter of the primary was determined on CT. The diagnostic sensitivity for detecting PPGL lesions was assessed visually and with a TBR threshold > 2. Lesion- and patient-based sensitivities were calculated. Subgroups were compared using non-parametric tests with multiplicity control. 69 patients presenting with 86 tumour lesions were analyzed. Patient-based sensitivity was 97.1% (67/69; 95%-CI 89.9-99.7) and lesion-based sensitivity 94.2% (81/86; 95%-CI 87.0-98.1%). Lesion-based sensitivity was 96.3% in non-metastatic disease (77/80; 95%-CI 89.4-99.2%) and 66.7% in metastatic disease [4/6; 95%-CI 22.3-95.7%]). Quantitative analysis showed a high image contrast (median TBR: 6.9). Cluster 2 showed less uptake intensity than sporadic, cluster 1a and cluster 1b tumours (TBR/SUV_mean/SUV_max, p = 0.003-0.025). MTV was larger in cluster 1b and sporadic cases than in cluster 2 (p = 0.011-0.018), whereas tumour diameter on CT did not differ between groups (p = 0.086-0.927). [¹⁸F]FDOPA PET/CT provides excellent image contrast in non-metastasized PPGL and can differentiate between varying genetic clusters, while morphological imaging failed for subtype segregation.