In vivo a-generator radionuclides such as 225Ac can deliver multiple a-particles to a single receptor site, dramatically amplifying the delivered radiotherapeutic dose. In this case, conventional bioconjugate constructs are of limited use as the high recoil energy of the daughters severs metal-ligand bonds, separating a-emitting daughters from the targeting agent. In this work, we demonstrate that a multilayered nanoparticle-antibody conjugate can deliver multiple a radiations from 225Ac at a receptor site.  This approach combines the radiation resistance of crystalline lanthanide phosphate to encapsulate and sequester 225Ac and its decay daughters; the magnetic properties of gadolinium phosphate for ease of separation; and the established surface chemistry of gold for attachment of targeting antibodies to nanoparticles. The nanoparticles were characterized by electron microscopy, radiotracer measurements, and neutron activation analysis. Nanoparticles conjugated to mAb 201b (thrombomodulin receptor) were used to determine biodistribution, pathology, and treatment efficacy on a murine EMT-6 tumor model.

Synthesis and characterization of multilayer Ln(<sup>225</sup>Ac )PO<sub>4</sub> nanoparticles for targeted alpha therapy

245th National Meeting (2013)

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Synthesis and characterization of multilayer Ln(225Ac )PO4 nanoparticles for targeted alpha therapy

Synthesis and characterization of multilayer Ln(²²⁵Ac )PO₄ nanoparticles for targeted alpha therapy