Sobol Nicholas, Sutherlin Logan, Cedrowska Edyta, Schorp Joshua, Rodríguez-Rodríguez Cristina, Sossi Vesna, Lattimer Jimmy, Miller Douglas C, Pevsner Paul, Robertson J David
Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
Department of Chemistry, University of Missouri, Columbia, Missouri 65211, USA.
APL Bioeng. 2017 Dec 27;2(1):016101. doi: 10.1063/1.5018165. eCollection 2018 Mar.
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 Lu. [Lu]LuGd(PO)@Au@PEG@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 Lu 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.
靶向放射疗法可使对癌细胞的细胞毒性最大化。在本研究中，我们描述了含镥的抗体偶联金包覆镧系磷酸盐纳米颗粒的合成、表征及生物分布。[镥]镥钆（磷酸）@金@聚乙二醇@抗体纳米颗粒结合了结晶镧系磷酸盐的抗辐射性以确保稳定性、钆的磁性以实现轻松分离，以及可轻松功能化以连接靶向部分的金涂层。与当前的靶向放射治疗药物不同，纳米颗粒 - 抗体偶联物可靶向并向单个生物学相关受体递送多种β射线。使用单克隆抗体mAb - 201b将纳米颗粒靶向血栓调节蛋白受体时，高达95%的注射剂量被递送至肺部。镥衰变产生的208 keVγ射线（11%）可用于放射治疗剂的单光子发射计算机断层扫描（SPECT）成像，而衰变过程中发射的中等能量β射线在治疗转移性疾病方面可能非常有效。
