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/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT inn= 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 (allp> 0.529). In contrast, the [18F]FDG PET/CT-derived 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.
背景/目的：采用α发射体[225Ac]Ac-PSMA-617增强[177Lu]Lu-PSMA-617放射性配体治疗的串联疗法，是晚期转移性去势抵抗性前列腺癌（mCRPC）中一种前景广阔的强化治疗方案。本研究评估了[18F]FDG PET/CT衍生的分子影像生物标志物在33例对[177Lu]Lu-PSMA-617单药治疗反应不足的患者中，预测PSMA串联放射性配体治疗（RLT）反应和预后的价值。方法：在基线期（即启动PSMA串联RLT前）测试了六种不同的分子影像参数（SUVmax、SUVpeak、SUV5、SUVmean、代谢肿瘤体积[MTV]和总病灶糖酵解[TLG]）与治疗反应及总生存期（OS）的关联性。结果：强化治疗启动后，24.2%既往反应不足的患者达到部分缓解，39.4%实现疾病稳定。中位OS为7个月（95% CI：4-11个月）。所有测试参数均未能预测治疗反应（所有p>0.529）。相比之下，[18F]FDG PET/CT衍生的全身分子影像参数TLG与[177Lu]Lu-PSMA-617单药治疗反应不足后接受[225Ac]Ac-PSMA-617增强[177Lu]Lu-PSMA-617 RLT患者的OS显著相关（p=0.029）。结论：在临床实践中将[18F]FDG PET/CT纳入PSMA-RLT管理，可能有助于预后预测，并为mCRPC患者提供更个体化的治疗路径。
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