18F-FLT PET/CT in the evaluation of pheochromocytomas and paragangliomas: A pilot study

Abstract

18F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare 18F-FLT uptake with 18F-FDG PET/CT, and to evaluate classic factors of aggressiveness. Methods: Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with 18F-FDG and 18F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. 18F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHBmutated status, lesion size, dopaminergic phenotype) and with 18FFDG uptake. Results: In 12 patients, 77 lesions were assessed. All lesions had low 18F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of 18F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high 18F-FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low 18F-FLT uptake. Conclusion: This study suggests that PHEOs/PGLs-even those that progress-do not exhibit intense 18F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of 18F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors.