Developmental Research Pilot Project

Scott Wilbur, PhD, University of Washington

"Targeted Alpha Therapy for Treatment of Metastatic Prostate Cancer in Bone"

Abstract

These pilot studies are designed to gain preliminary data on the therapeutic efficacy of the highly cytotoxic-particle emitting radionuclide At-211 targeted to metastatic prostate cancer cells in a mouse model. In the studies, two methods of selectively targeting the At-211 to prostate cancer cells using an anti-PSMA antibody, 107-1A4, will be evaluated. One method will involve coupling the At-211 to an intact mAb and injecting it. A second method will be to use a "two step" targeting approach, often referred to as "pretargeting". In that method the mAb will be biotinylated, injected and allowed to localize to the metastatic prostate cancer cells (e.g. 48h). Following that period, a biotin-binding protein, avidin, will be injected to clear the blood of excess biotinylated antibody, then At-211-labeled recombinant streptavidin (rSAv) will be injected. The rationale to including the At-211-labeled rSAv is that its molecular size is approximately 1/3 (~53 kDa) that of the intact mAb (~150 kDa), allowing better access to small metastatic tumors during the short decay period of the At-211 (t1/2=7.2 h). The metastatic prostate cancer model that we will use employs human prostate cancer cells (LNCaP) implanted in tibia of SCID mice. The effectiveness of the therapy will be monitored by assaying blood for the prostate-specific antigen (PSA) in the mice, routine radiography, and at sacrifice, tumor volume in bone. In an effective therapy, the PSA levels will be significantly lower than in the non-treated group and tumor volume will be lower.