Genetic status determines ¹⁸ F-FDG uptake in pheochromocytoma/paraganglioma

Introduction: Although few studies have demonstrated utility of ¹⁸ F- fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomography (¹⁸ F-FDG PET/CT) in benign pheochromocytoma/paragangliomas (PCC/PGLs), there limited data on factors predicting the FDG uptake in PCC/PGL.

Methods: The study was conducted at a tertiary health care centre. In addition to the routine investigations, all patients (n = 96) with PCC/PGL were evaluated with ¹⁸ F-FDGPET/CT and majority (n = 78) underwent ¹³¹ I-metaiodobenzyl guanidine (¹³¹ I-MIBG) scintigraphy. Forty-three patients also underwent testing for germline mutations in five PCC/PGL susceptibility genes (VHL, RET, SDHB, SDHC and SDHD) and all patients were evaluated clinically for neurofibromatosis-1.

Results: The study included 96 patients with PCC/PGL(82 benign and 14 malignant). FDGSUVmax was significantly higher for malignant than benign PCC/PGL(P = 0.009) and for extra-adrenal PGL than adrenal PCC (P = 0.017). In subgroup analysis, metanephrine-secreting PCC and non-secretory PCC had significantly lower FDG SUVmax than normetanephrine-secreting PCC (P = 0.017, P = 0.038 respectively), normetanephrine-secreting-sympathetic PGL (P = 0.008, P = 0.019 respectively) and non-secretory sympathetic PGL (P = 0.003, P = 0.009 respectively). Patients with mutations in cluster 1 genes (n = 14) had significantly higher FDG SUVmax than those with mutations in cluster 2 genes (n = 4) (P = 0.04). Sensitivities of ¹³¹ I-MIBG and ¹⁸ F-FDG PET/CTwere 77.78% and 100% for cluster 1 genes-related PCC/PGL whereas they were 100% and 50% for cluster 2 genes-related PCC/PGL, respectively. Multivariate regression analysis of mutation positive patients identified genetic status as the only independent predictor of FDG SUVmax.

Conclusion: The study suggests that the underlying genetic status determines FDG uptake in PCC/PGL and not location, secretory status or malignancy.