PET with Different Radiopharmaceuticals in Neuroendocrine Neoplasms: An Umbrella Review of Published Meta-Analyses

SIMPLE SUMMARY: Functional imaging methods and, in particular, positron emission tomography (PET) using several radiopharmaceuticals may play a pivotal role in patients with neuroendocrine neoplasms including neuroendocrine tumors (NETs) located in different sites, paraganglioma (PGL) and neuroblastoma (NB), recurrent medullary thyroid carcinoma (rMTC) and aggressive neuroendocrine neoplasms. Several radiopharmaceuticals can be used in this setting such as Gallium-68 somatostatin analogues ((68)Ga-SSA), Fluorine-18 fluorodihydroxyphenylalanine ((18)F-FDOPA), Gallium-68 exendin-4 ((68)Ga-exendin-4), Fluorine-18 fluorodeoxyglucose ((18)F-FDG). This umbrella review provides an evidence-based summary about meta-analyses on diagnostic performance, prognostic value, clinical impact and safety of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms. Overall, evidence-based data support the use of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms but with specific indications for each radiopharmaceutical. ABSTRACT: Background: Several meta-analyses have reported quantitative data about the diagnostic performance, the prognostic value, the impact on management and the safety of positron emission tomography (PET) including related hybrid modalities (PET/CT or PET/MRI) using different radiopharmaceuticals in patients with neuroendocrine neoplasms. We performed an umbrella review of published meta-analyses to provide an evidence-based summary. Methods: A comprehensive literature search of meta-analyses listed in PubMed/MEDLINE and Cochrane Library databases was carried out (last search date: 30 June 2021). Results: Thirty-four published meta-analyses were selected and summarized. About the diagnostic performance: (68)Ga-SSA PET yields high diagnostic performance in patients with NETs and PGL; (18)F-FDOPA PET yields good diagnostic performance in patients with intestinal NETs, PGL, NB, being the best available PET method in detecting rMTC; (68)Ga-exendin-4 PET has good diagnostic accuracy in detecting insulinomas; (18)F-FDG PET has good diagnostic performance in detecting aggressive neuroendocrine neoplasms. About the prognostic value: (68)Ga-SSA PET has a recognized prognostic value in well-differentiated NETs, whereas (18)F-FDG PET has a recognized prognostic value in aggressive neuroendocrine neoplasms. A significant clinical impact of (68)Ga-SSA PET and related hybrid modalities in patients with NETs was demonstrated. There are no major toxicities or safety issues related to the use of PET radiopharmaceuticals in patients with neuroendocrine neoplasms. Conclusions: Evidence-based data support the use of PET with different radiopharmaceuticals in patients with neuroendocrine neoplasms with specific indications for each radiopharmaceutical.