18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas

Abstract

Background: ¹⁸F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied. Methods: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent ¹⁸F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUV_max and SUV_mean] and the metabolic burden [MB] calculated as follows: MB = SUV_mean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry. Results: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUV_max ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01). Conclusion: While the ¹⁸F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that ¹⁸F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.

Somatostatin analogue pasireotide (SOM230) inhibits catecholamine secretion in human pheochromocytoma cells

“…Bovine chromaffin cells were cultured as previously described [33]. Human tumor cells were cultured from freshly resected Pheos following surgery [34]. In the operating room and J o u r n a l P r e -p r o o f immediately after the resection, the adrenal gland was cut longitudinally in two parts.…”

Dysfunction of exocytosis causes catecholamine hypersecretion in patient with pheochromocytoma

“…Human tumor cells were cultured from freshly resected Pheo following surgery (Moog et al, 2018). In the operating room and immediately after the resection, the adrenal gland was cut longitudinally in two parts.…”

11C-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma

“…Several nuclear medicine imaging tracers are available for positron emission tomography (PET)[11] and scintigraphy, including single-photon emission tomography (SPECT). The general PET-tracer 18 F-fluoro-deoxy-glucose ( 18 F-FDG) provides information on tumor metabolism [12], whereas more specialized tracers target specific pathways such as 123 I-meta-iodo-benzoguanidine ( 123 I-MIBG) [13] for scintigraphy, 18 F-dihydroxy-fluoro-L-phenylalanine ( 18 F-DOPA) [14,15,16,17,18,19], 18 F-Dopamine ( 18 F-DA) [20,21,22,23], 68 Ga-DOTA-somatostatin analogs [15,24,25,26,27] and 11 C- hydroxy ephedrine ( 11 C-HED) [28,29,30,31,32] for PET/CT. 11 C-HED is a norepinephrine analog that binds to the norepinephrine transporter and has previously shown high diagnostic sensitivity and specificity in patients with PCC/PGL [28], including post-operative surveillance following PCC/PGL resection [29] as well as for other tumors such as neuroblastoma [33,34].…”