¹⁸F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study

Abstract

Context 18F-FDG PET/CT has been proved 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. Objectives 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 classical factors of aggressiveness. Patients and Methods Twelve patients (7 metastatic and 5 non-metastatic) were prospectively evaluated with 18F-FDG and 18F-FLT and followed for at least 2 years after the initial imaging work-up. Outcome measures Uptake was assessed at a lesion level, visually and quantitatively by maximum standard uptake values (SUVmax) for both tracers. 18F-FLT uptake was compared to risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with 18F-FDG 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. Conclusions 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 biological behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors.

Leptomeningeal dissemination of a low-grade lumbar paraganglioma: case report

“…There was no superiority of 18 F-FLT uptake in progressive lesions suggesting the possibility that proliferation may not be a major indicator of aggressiveness. 19 Genetic biomarkers are also being developed as prognostic indicators. A recent study demonstrated that 53% of patients with at least one extra-adrenal paraganglioma had an identified germline mutation.…”

Personalized molecular visualization and radiotheranostics of adrenal tumors

“…Ряд исследований отметили более низкую чувствительность 18 F-FLT ПЭТ/КТ для ПГ, высокодифференцированных НЭО желудочно-кишечного тракта (ЖКТ), метастазоввысокодифференцированного рака щитовидной железы, а также первичного очага папиллярного рака щитовидной железы, по сравнению с 18 F-ФДГ ПЭТ/КТ, что, вероятно, связано с низкой пролиферативной активностью данных образований [86][87][88]. Blanchet et al продемонстрировали подгруппу ФХ и ПГ с высоким индексом Ki-67 и метастазами низкой пролиферативной активности [89]. Низкий уровень захвата 18 F-FLT отражает низкую эффективность антипролиферативных препаратов среди подобных опухолей.…”

Molecular imaging with FLT: a case of Cassandra’s curse?

“…Accordingly, its role in detecting sites of disease is compromised in an era when somatostatin receptor imaging, combined with FDG PET/CT for higher-grade NEN, has become a routine part of the diagnostic paradigm, at least in some parts of the world [9]. Similarly, in metastatic phaeochromocytoma/ paraganglioma, FLT uptake was minimal in even progressive lesions compared to FDG [10].…”