Value proposition of PSMA-targeted α–particle radioligand therapy in metastatic prostate cancer

Excerpt

Theranostics is currently experiencing a renaissance since the early days of radioiodine use in thyroid diseases. While there have been prior clinical platforms for theranostics (e.g., lymphoma, neuroblastoma), the recent regulatory approval and reimbursement of paired agents for somatostatin receptor-targeted theranostics of neuroendocrine tumors has helped to enrich the field [1]. Exciting developments are currently underway in theranostics of metastatic castrate-resistant prostate cancer (mCRPC), with prostate-specific membrane antigen (PSMA) as the biological target. Despite some limitations with nonspecificity, small molecule inhibitors binding to the external moiety of PSMA and radiolabeled with ⁶⁸Ga- (e.g. PSMA-11, PSMA-617, PSMA I&T) or ¹⁸F- (e.g. DCFPyL, PSMA-1007) have demonstrated excellent diagnostic imaging performance and competitive advantage over other non-PSMA based radiotracers [2]. When radiolabeled with β-emitters (e.g., ¹⁷⁷Lu, ¹³¹I) or α-emitters (e.g., ²²⁵Ac, ²¹³Bi), particular PSMA-based agents can also be used for targeted radiotherapy of the same metastatic lesions that are identified by the imaging companion agent realizing the bidirectional “see & treat” concept [3‐9]. …