Liver Background Uptake of Prostate-specific Membrane Antigen-targeted PET Radiotracers: A Systematic Review and Meta-Analysis.

Purpose To perform a systematic review and meta-analysis of liver background uptake across four prostate-specific membrane antigen (PSMA)-targeting PET radiotracers (fluorine 18 [18F]-piflufolastat, gallium 68 [68Ga]-PSMA-11, 18F-flotufolastat, and 18F-PSMA-1007) and evaluate the potential impact on patient selection for PSMA-targeted therapy. Materials and Methods A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane through May 12, 2025, to identify human studies reporting quantitative liver background uptake for the four PSMA-targeted PET radiotracers of interest. For each eligible study, liver background uptake was extracted as standardized uptake values (SUVs) and summarized and compared by radiotracer using random effects models with robust variance estimation. Results Among 652 unique records, 17 studies with 1497 total patients met inclusion criteria and reported liver background SUVs. Summary mean liver background SUV was 5.0 (95% CI: 3.6, 6.3) for 18F-piflufolastat, 5.1 (95% CI: 4.3, 5.9) for 68Ga-PSMA-11 (P = .579 compared with 18F-piflufolastat), 7.2 (95% CI: 6.3, 8.2) for 18F-flotufolastat (P = .005), and 12.1 (95% CI: 11.4, 12.9) for 18F-PSMA-1007 (P < .001). Conclusion Liver background uptake differed across PSMA-targeted PET radiotracers and may influence patient eligibility for PSMA-targeted therapy when liver activity is used as a reference for defining PSMA-positive metastatic prostate cancer. Keywords: PET, Genital/Reproductive, Prostate, 68Ga-PSMA-11, 18F-piflufolastat, 18F-flotufolastat, 18F-PSMA-1007, PSMA-targeted PET, PSMA-targeted Therapy Supplemental material is available for this article. © RSNA, 2026.