Engineered Liposomes for Potential -Particle Therapy of Metastatic Cancer

Disseminated, metastatic cancer is frequently incurable. Targeted -particle emitters hold great promise as therapeutic agents for dis-seminated disease. 225Ac is a radionuclide generator that has a 10-d half-life and results in -emitting daughter elements (221Fr, 217At, 213Bi) that lead to the emission of a total of 4 -particles. The aim of this study was to develop approaches for stable and controlled targeting of 225Ac to sites of disseminated tumor metastases. Liposomes with encapsulated 225Ac were developed to retain the potentially toxic daughters at the tumor site. Methods: 225Ac was passively entrapped in liposomes. To experimentally test the retention of actinium and its daughters by the liposomes, the -emissions of 213Bi were measured in liposome fractions, which were separated from the parent liposome population and the free radionuclides, at different times. Under equi-librium conditions the decay rate of 213Bi was used to determine the concentration of 225Ac. Measurements of the kinetics of 213Bi activit