Gold-coated lanthanide phosphate nanoparticles for an ~(225)Ac in vivo alpha generator

摘要

Retaining radioactive daughter products at a clinically relevant target site remains one of the major challenges in development of in vivo α generators with radionuclides such as ~(225)Ac and ~(223)Ra. In this work, we examine the ability of layered nanoparticle constructs to retain ~(225)Ac and the first decay daughter, ~(221)Fr. Actinium-225 is cocrystalized in a lanthanide phosphate nanoparticle consisting of varying amounts of La and Gd. Additional lanthanide phosphate layers improve retention capability while an outer layer of gold facilitates the attachment of targeting moieties for in vivo use. Retention of ~(225)Ac in the nanoparticles is near quantitative while the ~(221)Fr retention varies from 60-89% as a function of time, the number of layers, and nanoparticle composition. Decay corrected radiochemical yield in the multi-shell syntheses are high (76%) and comparable to or better than existing delivery approaches.