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

Nicholas Sobol; Logan Sutherlin; Edyta Cedrowska; Joshua Schorp; Cristina Rodríguez-Rodríguez; Vesna Sossi; Jimmy Lattimer; Douglas C Miller; Paul Pevsner; J David Robertson

doi:10.1063/1.5018165

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

APL Bioeng. 2017 Dec 27;2(1):016101. doi: 10.1063/1.5018165. eCollection 2018 Mar.

Authors

Nicholas Sobol, Logan Sutherlin, Edyta Cedrowska¹, Joshua Schorp², Cristina Rodríguez-Rodríguez, Vesna Sossi³, Jimmy Lattimer⁴, Douglas C Miller⁵, Paul Pevsner⁶, J David Robertson

Affiliations

¹ Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
² Department of Chemistry, University of Missouri, Columbia, Missouri 65211, USA.
³ Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
⁴ Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri 65211, USA.
⁵ Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
⁶ Nano Imrad Technology, Inc., Irving, Texas 75039, USA.

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]Lu_0.5Gd_0.5(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.