Abstract
Purpose: Recently, an 211At-labeled RGD peptide with an albumin-binding moiety, Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]1), was developed for targeted alpha therapy and radiotheranostics. [211At]1 showed high tumor accumulation and inhibited tumor growth in a dose-dependent manner. This study aimed to investigate whether [211At]1 can induce an antitumor immune response and whether the combination of [211At]1 and immune checkpoint blockade can enhance therapeutic efficacy. Methods: Biodistribution experiments of [211At]1 and therapeutic experiments of [211At]1 with or without anti-PD-1 or anti-CTLA-4 antibody were conducted in Colon-26 tumor-bearing BALB/c mice. Additionally, therapeutic experiments of [211At]1 were conducted in Colon-26 tumor-bearing BALB/c nu/nu mice to confirm the difference in the therapeutic effects derived from antitumor immune responses of [211At]1. Infiltration of antitumor immune activity in Colon-26 tumors was confirmed by flow cytometry and immunofluorescence staining. Results: [211At]1 showed high tumor accumulation and inhibited tumor growth in a dose-dependent manner in Colon-26 tumor-bearing BALB/c mice. Additionally, mice treated with [211At]1 (675 kBq) and anti-CTLA-4 antibody showed superior tumor growth inhibition compared with mice treated with only [211At]1 (675 kBq). Tumor growth inhibition was weaker in BALB/c nu/nu mice than in BALB/c mice. Infiltration of CD4+ and CD8+ T cells was observed following treatment with [211At]1 (675 kBq) alone or in combination with anti-CTLA-4 antibody. Conclusion: [211At]1 induced an antitumor immune response and enhanced the therapeutic efficacy. The combination of [211At]1 and immune checkpoint blockade agents could be promising for cancer therapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s00259-025-07498-3.