Targeted Delivery of Alpha Particle-Emitting Radionuclides and Their Alpha-Emitting Progeny: Breast Cancer Therapy Using Lipsome Encapsulated Alpha Emitters

Abstract : This concept award was extended by a year over the initial one-year period at no additional cost. The primary objective is to investigate liposomal encapsulation of chelated Ac-225 in order to reduce loss of progeny from the targeting vehicle and, therefore, the tumor site. Results have shown that the extent of daughter retention is dependent upon liposomal vesicle diameter with larger vesicles retaining the alpha- particle emitting daughters to a greater extent. The dependence of retention on the diameter of the liposomal vesicle is thought to arise because of recoil of the daughter nuclei. The recoil distance of daughter nuclei after alpha-particle emission is approximately 100 nm. Depending upon the site of decay, therefore, the recoil distance is sufficient to eject the daughter outside of the liposome. Assuming that ejection by recoil is the only mechanism by which daughters escape from the vesicles, a theoretical model relating vesicular diameter with daughter retention has been developed. Measured retention values do not fall within model predictions. Upcoming studies will focus on understanding the observed divergence between model-predicted and observed retention and also on carrying out animal studies evaluating loco-regional therapy with larger vesicles.