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