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[225Ac]hu11B6-IgG1H435A is a research-stage targeted alpha-particle radioimmunotherapy (TAT) agent. It consists of the humanized monoclonal antibody hu11B6, which targets human kallikrein 2 (hK2; KLK2), a prostate-specific serine protease. This specific variant utilizes an IgG1 scaffold with an H435A mutation in the Fc region, which abolishes binding to the neonatal Fc receptor (FcRn), thereby preventing FcRn-mediated recycling and internalization. The antibody is conjugated to the alpha-emitting radioisotope Actinium-225 (225Ac) via a DOTA chelator. Developed by Diaprost AB, it has been used in preclinical studies as a non-internalizing mechanistic comparator to the native [225Ac]hu11B6-IgG1 to evaluate the impact of cellular internalization on the therapeutic efficacy of alpha-radioimmunotherapy in prostate cancer models.
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