225Ac-DOTA-YS5 is a CD46-targeted PET Radiopharmaceutical under evaluation for therapeutic use in prostate cancer. YS5, is a fully human, full-length IgG1, selected from phage antibody display libraries. YS5 demonstrated high-Affinity binding to prostate cancer cell and tissue, with little or no binding to normal tissues. CD46 was identified as the target bound by the antibody. CD46 is known to be a negative regulator of the complement cascade in the innate immune system. In contrast with lineage markers, such as PSMA, CD46 shows uniformly intense cell surface expression in dedifferentiated castration-resistant prostate cancer phenotypes, including both adenocarcinoma and treatment-emergent neuroendocrine prostate cancer. 225Ac-DOTA-YS5 is paired with the Imaging agent 89Zr-DFO-YS5 which entered Phase I clinical trial in 2022.

Target/Mechanism: CD46

Carrier/Ligand: IgG1

Radiation Type: Alpha particle (α)