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

The augmentation of [ Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [ Ac]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 [ F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in = 33 patients with insufficient response on [ Lu]Lu-PSMA-617 monotherapy. Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUV , SUV , SUV , SUV , metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). 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 > 0.529). In contrast, the [ F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly ( = 0.029) associated with OS of patients undergoing [ Ac]Ac-PSMA-617 augmented [ Lu]Lu-PSMA-617 RLT after insufficient response to [ Lu]Lu-PSMA-617 monotherapy. Implementing [ F]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.