225Ac-DOTA-daratumumab

225Ac-DOTA-daratumumab is an investigational alpha-particle emitting radioimmunotherapy (RIT) agent developed by City of Hope Medical Center for the treatment of relapsed or refractory multiple myeloma. The drug consists of the anti-CD38 monoclonal antibody daratumumab conjugated to the radionuclide Actinium-225 via a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelator. By targeting CD38, a protein highly and uniformly expressed on the surface of multiple myeloma cells, the conjugate delivers high-energy, short-range alpha radiation directly to the tumor site. This targeted radiation induces complex DNA double-strand breaks and subsequent cell death. Unlike unconjugated daratumumab, which relies on immune-mediated effector functions like ADCC and CDC, 225Ac-DOTA-daratumumab is designed to be effective even in patients who have become refractory to standard daratumumab therapy due to immune exhaustion or other resistance mechanisms. It is currently being evaluated in Phase 1 clinical trials (NCT05363111) at City of Hope.

Other names

actinium Ac 225-DOTA-daratumumab225Ac-DOTA-DaratumumabAc-225-DOTA-daratumumabAc225-DOTA-daratumumabAc 225-DOTA-daratumumab