Synthesis and targeting of gold-coated 177Lu-containing lanthanide phosphate nanoparticles—A potential theranostic agent for pulmonary metastatic disease

Abstract

Targeted radiotherapies maximize cytotoxicity to cancer cells. In this work, we describe the synthesis, characterization, and biodistribution of antibody conjugated gold-coated lanthanide phosphate nanoparticles containing 177Lu. [177Lu]Lu0.5Gd0.5(PO4)@Au@PEG800@Ab nanoparticles combine the radiation resistance of crystalline lanthanide phosphate for stability, the magnetic properties of gadolinium for facile separations, and a gold coating that can be readily functionalized for the attachment of targeting moieties. In contrast to current targeted radiotherapeutic pharmaceuticals, the nanoparticle-antibody conjugate can target and deliver multiple beta radiations to a single biologically relevant receptor. Up to 95% of the injected dose was delivered to the lungs using the monoclonal antibody mAb-201b to target the nanoparticles to thrombomodulin receptors. The 208 keV gamma ray from 177Lu decay (11%) can be used for SPECT imaging of the radiotherapeutic agent, while the moderate energy beta emitted in the decay can be highly effective in treating metastatic disease.