Prospective Intraindividual Comparison of Ga-68 PSMA and F-18 FDG Dual-Tracer PET/CT Imaging in Evaluation of High-Grade Prostate Cancer.

INTRODUCTION: High-grade prostate cancer (International Society of Urological Pathology [ISUP] grade groups 4 and 5) is often aggressive and associated with early metastatic spread. Gallium-68 (Ga-68) prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is widely adopted for prostate cancer imaging due to its high sensitivity, while F-18 fluorodeoxyglucose (FDG) PET/CT may provide complementary metabolic information. This study investigates and compares the diagnostic performance of these two modalities and evaluates the incremental value of dual-tracer PET/CT imaging. METHODS: This prospective observational study included 51 patients with biopsy-proven, high-grade prostate adenocarcinoma (ISUP grade groups 4 and 5) undergoing both Ga-68 PSMA and F-18 FDG PET/CT within 1 week. Detection rates for primary tumors, nodal, and distant metastases were analyzed. Maximum standardized uptake values (SUVmax), lesion-to-aorta and lesion-to-muscle ratios, and serum prostate-specific antigen (PSA) levels were correlated. RESULTS: Ga-68 PSMA PET/CT demonstrated superior detection rate for primary tumor detection (90.2%) compared to F-18 FDG PET/CT (66.7%, p  = 0.004). For pelvic lymph nodes, detection rates were numerically higher with PSMA PET/CT (76.2% vs. 59.5% for FDG PET/CT), although this difference did not reach statistical significance; for extrapelvic lymph nodes, 95.2% (PSMA) versus 52.4% (FDG, p  = 0.02); and for bone lesions, 100% (PSMA) versus 77.8% (FDG, p  = 0.009). In ISUP grade 4, primary detection was 94.4% (PSMA) versus 50% (FDG, p  = 0.003); in grade 5, 87.9% (PSMA) versus 75.8% (FDG). Dual-tracer imaging improved overall detection of primary tumors and pelvic lymph nodes to 100 and 90.4%, respectively. A mild correlation was observed between PSA levels and PSMA SUVmax ( r  = 0.297, p  = 0.034). Strong positive correlations were found between SUVmax and both lesion-to-aorta and lesion-to-muscle ratios for both tracers. Interreader agreement was excellent for PSMA ( κ  = 1.00) and high for FDG ( κ  = 0.95). CONCLUSION: Ga-68 PSMA PET/CT demonstrated high detection rates for detecting primary and metastatic lesions in high-grade prostate cancer. F-18 FDG PET/CT offers complementary metabolic information, particularly valuable in ISUP grade 5 and dedifferentiated tumors. Dual-tracer PET/CT enhances diagnostic accuracy and may facilitate personalized treatment strategies in aggressive prostate cancer.