Metabolic Subtyping of Pheochromocytoma and Paraganglioma by ¹⁸F-FDG Pharmacokinetics Using Dynamic PET/CT Scanning.

Abstract

Static single-time-frame ¹⁸F-FDG PET/CT is useful for the localization and functional characterization of pheochromocytomas and paragangliomas (PPGLs). ¹⁸F-FDG uptake varies between PPGLs with different genotypes, and the highest SUVs are observed in cases of succinate dehydrogenase (<i>SDH</i>) mutations, possibly related to enhanced aerobic glycolysis in tumor cells. The exact determinants of ¹⁸F-FDG accumulation in PPGLs are unknown. We performed dynamic PET/CT scanning to assess whether in vivo ¹⁸F-FDG pharmacokinetics has added value over static PET to distinguish different genotypes. <b>Methods:</b> Dynamic ¹⁸F-FDG PET/CT was performed on 13 sporadic PPGLs and 13 PPGLs from 11 patients with mutations in <i>SDH</i> complex subunits B and D, von Hippel-Lindau (<i>VHL</i>), <i>RET,</i> and neurofibromin 1 (<i>NF1</i>). Pharmacokinetic analysis was performed using a 2-tissue-compartment tracer kinetic model. The derived transfer rate-constants for transmembranous glucose flux (<i>K</i>₁ [in], <i>k</i>₂ [out]) and intracellular phosphorylation (<i>k</i>₃), along with the vascular blood fraction (V_b), were analyzed using nonlinear regression analysis. Glucose metabolic rate (MR_glc) was calculated using Patlak linear regression analysis. The SUV_max of the lesions was determined on additional static PET/CT images. <b>Results:</b> Both MR_glc and SUV_max were significantly higher for hereditary cluster 1 (<i>SDHx, VHL</i>) tumors than for hereditary cluster 2 (<i>RET, NF1</i>) and sporadic tumors (<i>P</i> < 0.01 and <i>P</i> < 0.05, respectively). Median <i>k</i>₃ was significantly higher for cluster 1 than for sporadic tumors (<i>P</i> < 0.01). Median V_b was significantly higher for cluster 1 than for cluster 2 tumors (<i>P</i> < 0.01). No statistically significant differences in <i>K</i>₁ and <i>k</i>₂ were found between the groups. Cutoffs for <i>k</i>₃ to distinguish between cluster 1 and other tumors were established at 0.015 min^-1 (100% sensitivity, 15.8% specificity) and 0.636 min^-1 (100% specificity, 85.7% sensitivity). MR_glc significantly correlated with SUV_max (<i>P</i> = 0.001) and <i>k</i>₃ (<i>P</i> = 0.002). <b>Conclusion:</b> In vivo metabolic tumor profiling in patients with PPGL can be achieved by assessing ¹⁸F-FDG pharmacokinetics using dynamic PET/CT scanning. Cluster 1 PPGLs can be reliably identified by a high ¹⁸F-FDG phosphorylation rate.