Reducing renal uptake of free 213Bi associated with the decay of 225Ac-labeled radiopharmaceuticals

Alpha-emitting radionuclides provide cytotoxic agents that are considered impervious to conventional cellular resistance mechanisms such as effusion pumps, signaling pathway redundancy, and cell cycle modulation (e.g., cell dormancy, G1/G0 or G2/M block). Actinium-225 is a promising α-emitting radionuclide due to its net decay of four α-particles. The longest-lived progeny of 225Ac, bismuth-213 concentrates in the kidneys. Depending upon tumor burden, and the accessibility of tumor cells the percent tumor uptake of IV-administered radiolabeled antibody in humans is typically of the order of a few percent or less. This means that the majority of antibody-bound 225Ac decays would occur in the circulation and lead to eventual renal toxicity as has been observed in pre-clinical studies The objective of this work is to evaluate the potential to reduce renal uptake of free 213Bi by exploiting the mechanism associated with bismuth uptake.

NEDROW Jessie;  JOSEFSSON Anders;  PARK Sunju;  HOBBS Robert F.;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SGOUROS G.; 

2017-08-01

European Commission - Joint Research Centre

JRC106142