Analysis of Molecular Imaging Biomarkers Derived from [18F]FDG PET/CT in mCRPC: Whole-Body Total Lesion Glycolysis (TLG) Predicts Overall Survival in Patients Undergoing [225Ac]Ac-PSMA-617-Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy

Abstract

Background/Objectives: The augmentation of [177Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [225Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [18F]FDG PET/CTderived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [177Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUVmax, SUVpeak, SUV5 , SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [18F]FDG PET/CTderived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT after insufficient response to [177Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [18F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC.