Development of Novel Integrin α_vβ₃-Targeted Radioligand for Enhanced Tumor Accumulation

Effective tumor delivery of radioligands is crucial for cancer diagnosis and therapy. Integrin α_vβ₃ is an attractive target for cancer treatment, and the development of integrin α_vβ₃-targeted radioligands with high-level tumor accumulation is desired. Albumin binder (ALB) is a useful moiety to enhance tumor accumulation of radioligands. Furthermore, the introduction of dual amino acid linkers to an ALB-containing prostate-specific membrane antigen-targeted radioligand enhances the tumor accumulation by increasing its albumin-binding affinity. In this study, we newly developed two integrin α_vβ₃-targeted radioligands: one containing both dual amino acid linkers and ALB ([¹¹¹In]-In-RGD-DA6) and another containing only ALB ([¹¹¹In]-In-RGD-DA1). In albumin-binding assays, [¹¹¹In]-In-RGD-DA6 showed higher albumin-binding affinity than [¹¹¹In]-In-RGD-DA1 and [¹¹¹In]-In-DOTA-c-(RGDfK), a counterpart without dual amino acid linkers and ALB. In biodistribution studies, [¹¹¹In]-In-RGD-DA6 also showed higher tumor accumulation than [¹¹¹In]-In-RGD-DA1 and [¹¹¹In]-In-DOTA-c-(RGDfK). These results highlight the potential of [¹¹¹In]-In-RGD-DA6 as an integrin α_vβ₃-targeted radioligand with enhanced tumor accumulation.