Lanthanide-based Nanoparticles for Multimodal Molecular Imaging and Targeted Alpha Therapy

Abstract

To assess the in vitro retention of therapeutically relevant radionuclides such as in vivo α-generators Ra-223, Ac-225, and Th-227 in lanthanide phosphate (LnPO4) and lanthanide vanadate (LnVO4) core-shell nanoparticles (NPs) towards their promising application as multifunctional platforms in nanomedicine. LnPO4 and LnVO4 core-shell NPs doped with either Eu-156, a radionuclide “cocktail” of Sr-85, Sr-89, Eu-156, or in vivo α-generators Ra-223, Ac-225, and Th-227 were synthesized in aqueous media. In vitro retention of radionuclides was assessed by dialyzing the radioactive NPs suspensions against deionized water and quantifying the activity in dialysate aliquots over time using a high purity germanium detector. The crystal structure, morphology, colloidal stability, luminescence and magnetic properties of LnPO4 and LnVO4 core-shell NPs were evaluated. Partial retention of Eu-156 (∼70–95%) and Sr-85 (>80%) was evidenced in LnPO4 core NPs, while Th-227 and decay daughters were retained quantitatively (>99%) in LaPO4 core-shell NPs. Gd0.8Eu0.2VO¬4 and GdVO4 core-shell NPs showed partial retention of Ra-223 (∼75 %), Ac-225 (75–95%), and Th-227 (>96%). Retention of decay daughters in LnVO4 NPs was enhanced after deposition of nonradioactive shells. Adjusting the lanthanide concentration provided luminescence and magnetic properties for fluorescence and magnetic resonance imaging. Emission intensities were higher for LnVO4 NPs with respect to LnPO4, whereas no significant difference was observed in the magnetic susceptibility. GdVO4 core NPs displayed enhancement of the signal intensity of T1-weighted images. This work evidences the potential application of LnPO4 and LnVO4 core-shell NPs as platforms for multimodality molecular imaging and targeted alpha therapy. Partial retention of radionuclides may enhance the efficacy of treatment while minimizing the dose delivered to healthy organs. Radionuclide retention was influenced by the lanthanide concentration, the crystal structure, and the number of shells added.