Leveraging Bioorthogonal Click Chemistry to Improve ²²⁵Ac-Radioimmunotherapy of Pancreatic Ductal Adenocarcinoma.

ABSTRACT:

Purpose

Interest in targeted alpha-therapy has surged due to α-particles' high cytotoxicity. However, the widespread clinical use of this approach could be limited by on-/off-target toxicities. Here, we investigated the inverse electron-demand Diels-Alder ligation between an ²²⁵Ac-labeled tetrazine radioligand and a trans-cyclooctene-bearing anti-CA19.9 antibody (5B1) for pretargeted α-radioimmunotherapy (PRIT) of pancreatic ductal adenocarcinoma (PDAC). This alternative strategy is expected to reduce nonspecific toxicities as compared with conventional radioimmunotherapy (RIT).Experimental Design: A side-by-side comparison of ²²⁵Ac-PRIT and conventional RIT using a directly ²²⁵Ac-radiolabeled immunoconjugate evaluates the therapeutic

SUBMITTER: Poty S 

PROVIDER: S-EPMC6343144 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature