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Simple Summary  Functional imaging with  18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) has evolved into a major clinical tool in cancer diagnosis and management for many malignancies in diverse clinical settings, providing valuable information on tumor behavior and aggressiveness. In the field of neuroendocrine tumors (NETs), recent advances in molecular imaging and targeted treatments with novel theranostic agents favor a more patient-tailored approach. Although peptide receptor radionuclide therapy (PRRT) has recently become an established therapy for progressive NETs, the role of  18 F-FDG PET prior to PRRT in patients with NETs of different origins and grades remains to be determined. Herein, we provide a comprehensive summary of available evidence in contemporary literature by means of a systematic review and meta-analysis, demonstrating that dual-functional imaging with  68 Ga-DOTA-peptides and  18 F-FDG prior to PRRT appears to be a useful tool in NET management by delineating tumor somatostatin receptor expression and glycolytic metabolic activity, and predicting tumor response and survival outcomes.    Abstract  The role of  18 F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of  18 F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative  18 F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive  18 F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative  18 F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion,  18 F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis