Variable cellular and radiobiological effects of [177Lu]Lu-PSMA-I&T in patient-derived models of prostate cancer

Abstract

Background: [177Lu]Lu-PSMA radioligand therapy targets metastatic castration-resistant prostate cancer by delivering radiation to cells expressing prostate-specific membrane antigen (PSMA). While some patients show remarkable responses, up to 50% show little to no benefit, and disease progression inevitably occurs. Eligibility is mainly based on PSMA avidity by PET imaging, yet responses remain highly variable, highlighting a disconnect between PSMA expression and clinical efficacy. This study used PSMA-positive patient-derived xenografts (PDXs) from the Melbourne Urological Research Alliance (MURAL) to explore mechanisms of response and resistance to [177Lu]Lu-PSMA treatment. Methods: PDXs ..