In vitro evaluation of anti-HIV radioimmunoconjugates labeled with astatine-211, thorium-227 and actinium-225.

We conducted an in vitro investigation of the selective cytotoxicity of alpha-emitting radioimmunoconjugates (α-RICs) directed against cells expressing HIV envelope (Env) proteins. It is well known that monoclonal antibody (mAb)-targeted α-emitting radionuclides can effectively kill antigen-expressing cells; however, the expected low-level expression of HIV antigens on latently infected cells poses an obstacle to all anti-HIV immune-based treatments, including α-RICs. This investigation tested the cytotoxicity of the HIV envelope antigen-binding mAbs, PGT126 (binding gp120) and 7B2 (binding gp41), conjugated with labeling chelators that bind the α-emitters astatine-211 ((211)At), actinium-225 ((225)Ac) or thorium-227 ((227)Th). METHODS: High specific activity (SA) preparations of the α-RICs were made to increase the proportion of mAb conjugates carrying the α-emitting isotope. RIC cytolytic activity was evaluated against a cell line stably expressing the HIV envelope. RESULTS: (211)At-labeled mAb conjugates did not demonstrate specific cell killing, while the longer lived radiometal α-RICs, (227)Th and (225)Ac, efficiently and specifically killed HIV envelope expressing cells. CONCLUSIONS: Potential explanations for these differential effects include the longer half-lives of (225)Ac and (227)Th compared to (211)At and differences in the decay properties of radiometals compared to radiohalogens. These encouraging in vitro results suggest that in vivo evaluations of α-RIC in depleting the HIV harboring cells are warranted.