@article {KUHLMANN2026109602,
	title = {In vitro evaluation of anti-HIV radioimmunoconjugates labeled with astatine-211, thorium-227 and actinium-225},
	journal = {Nucl. Med. Biol.},
	year = {2026},
	pages = {109602},
	abstract = {<p>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 (211At), actinium-225 (225Ac) or thorium-227 (227Th). 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 211At-labeled mAb conjugates did not demonstrate specific cell killing, while the longer lived radiometal α-RICs, 227Th and 225Ac, efficiently and specifically killed HIV envelope expressing cells. Conclusions Potential explanations for these differential effects include the longer half-lives of 225Ac and 227Th compared to 211At 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.</p>},
	keywords = {Actinium-225, Astatine-211, HIV, Radioimmunotherapy, thorium-227},
	issn = {0969-8051},
	doi = {https://doi.org/10.1016/j.nucmedbio.2026.109602},
	url = {https://www.sciencedirect.com/science/article/pii/S0969805126000016},
	author = {Anne-Sophie Kuhlmann and Donald K. Hamlin and Yawen Li and Xinyi Wang and Lily Li and Chris Orvig and Hans-Peter Kiem and Brenda M. Sandmaier and D. Scott Wilbur and Seth Pincus and Robert D. Harrington}
}
