Long-Term Therapeutic Effects of ²²⁵Ac-DOTA-E[c(RGDfK)]₂ Induced by Radiosensitization via G2/M Arrest in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Background: Alpha radionuclide therapy has emerged as a promising novel strategy for cancer treatment; however, the therapeutic potential of ²²⁵Ac-labeled peptides in pancreatic cancer remains uninvestigated. Methods: In the cytotoxicity study, tumor cells were incubated with ²²⁵Ac-DOTA-RGD₂. DNA damage responses (γH2AX and 53BP1) were detected using flowcytometry or immunohistochemistry analysis. Biodistribution and therapeutic studies were carried out in BxPC-3-bearing mice. Results: ²²⁵Ac-DOTA-RGD₂ demonstrated potent cytotoxicity against cells expressing α_vβ₃ or α_vβ₆ integrins and induced G2/M arrest and γH2AX expression as a marker of double-stranded DNA breaks.

SUBMITTER: Yoshimoto M 

PROVIDER: S-EPMC11768328 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature