Fig. 1.

Pharmacokinetics and pharmacodynamics of [²²⁵Ac]hu11B6 in xenograft models of prostate cancer. Full [²²⁵Ac]hu11B6 biodistribution data set of (a) LNCaP-AR and (b) VCaP s.c. xenograft models, where the significantly higher tumor accumulation of [²²⁵Ac]hu11B6 can be noted in the VCaP model as a result of higher target expression. c Kaplan–Meier plot comparing survival of LNCaP-AR s.c. tumor models (n = 10 per group) treated with a single 300 nCi dose of [²²⁵Ac]hu11B6 (red line), 300 nCi non-internalizing hK2 targeting antibody [²²⁵Ac]hu11B6-H435A (blue line), or 300 nCi of an alpha-particle labeled non-specific antibody [²²⁵Ac]huIgG₁ (black line). These results demonstrate that effective hK2-targeted alpha particle delivery by hu11B6 depends on both antigen specificity and FcRn-mediated internalization of the immunoglobulin