Utility of Novel Radiohybrid PSMA Ligands in PET Imaging of Biochemical Recurrence of Prostate Cancer—A Systematic Review and Meta-analysis

Purpose Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a novel class of radiopharmaceuticals developed for potential theranostic application in prostate cancer (PCa). We aimed to consolidate existing evidence on utility of 18 F-rhPSMA-7/7.3 for PET imaging in PCa in the setting of biochemical recurrence (BCR). Patients and Methods A comprehensive literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles evaluating utility of 18 F-rhPSMA-7/7.3 PET in PCa BCR, published through September 30, 2024, were included. rhPSMA PET detection rate (DR) in BCR was calculated on a per-patient basis, with pooled proportion and 95% confidence interval. Furthermore, pooled DRs using different cutoff values of serum prostate-specific antigen (PSA) were obtained. Results Five studies with 1513 patients (overall) were included. The pooled DR of 18 F-rhPSMA-7/7.3 PET in BCR was 81.7% (95% confidence interval: 76.3%–86.5%). The pooled DRs stratified by serum PSA levels were 60.7% for PSA <0.5 ng/mL, 80.1% for PSA between 0.5 and <1.0 ng/mL, 85.9% for PSA between 1.0 and <2.0 ng/mL, and 95.1% for PSA ≥2.0 ng/mL, respectively. Conclusions Our results suggest that novel radiotracers 18 F-rhPSMA-7/7.3 have excellent diagnostic utility as PET imaging agents in BCR of PCa. Further prospective multicenter studies are required to validate these novel tracers in diverse clinical settings with larger patient cohorts and assess their diagnostic accuracy in comparison to the PSMA ligands in current clinical practice.