Preparation and testing of bevacizumab radioimmunoconjugates with Bismuth-213 and Bismuth-205 / Bismuth-206

Abstract

Bevacizumab, a humanized anti-VEGF monoclonal antibody has shown promise in various clinical trials. We report the development and testing of Bi-213 (an alpha-emitting radionuclide) labeled bevacizumab for in vitro and in vivo studies using two different chelators viz cDTPA and CHX-A″. The developed labeling method showed high labeling yields of 93.6% and 89.7% for cDTPA and CHX-A″ respectively and the results were reproducible. The in vitro and in vivo stability tests were carried out using Bi-213 and long half-life Bismuth isotope (Bi-205 / Bi-206) for pharmacokinetics. The in vitro results showed remarkable stability of the radiolabeled bevacizumab regardless of the chelator. The in vivo pharmacokinetics studies however, showed that the uptake and retention of cDTPA- bevacizumab was significantly higher in kidneys (p-value 0.02) and lower in liver and spleen (p-value