Pre-targeting of Astatine-211 fo rTherapy of Metastatic Prostate Cancer

Abstract : The purpose of this research project was to develop conditions and reagents required for effective targeting of the alpha-emitting radionuclide At-211 to metastatic prostate cancer cells. In the studies conducted, three different approaches to "pretargeting" At-211 to human prostate cancer xenografts were evaluated in athymic mice. One of the important questions asked was whether At-211 could be stably attached to a carrier molecule. The results obtained indicate that stable attachments can be obtained for certain types of compounds (i.e. nido-carboranes) but not for others (i.e. arylastatides) Effective tumor targeting was obtained in the studies, but higher than anticipated concentrations of reagents were found in non-target tissues. This finding may be due to the use of intact antibodies (Fc mediated binding). Another problem that became apparent was the fact that large quantities of biotin binding reagents (streptavidin or antibody-streptavidin conjugates) had to be used to offset the endogenous biotin released from body stores. The studies have help to delineate the requirements for pretargeting of At-211, but additional studies are required to optimize this approach.