Targeted α-therapy (TAT) is a promising treatment method for small tumors and metastases. The high linear energy transfer of α-particles causes double strand DNA breaks inducing cell death. With traditional chelators, the recoil effect during α-decay causes the chelation bonds to break. This is a problem for α-emitters that have long decay chains, like 225Ac, because daughter radionuclides are released from the tumor site. This decreases the dose delivered in the tumor site and increases the dose delivered to healthy tissue throughout the body. Silica nanoparticles are a promising solution as additional layers of silica can be added after radiolabeling, increasing the retention of daughter radionuclides in the tumor site. Another challenge in working with 225Ac is the inability to image the biological agent. Silica nanoparticles allow for the co-incorporation of PET radionuclide 89Zr and TAT radionuclide 225Ac resulting in a theragnostic agent. Silica nanoparticles are also cheap, biologically inert, and can be functionalized with peptides to target specific receptors expressed in tumors. Initial radiochemical studies used 140La as a chemical surrogate for 225Ac. The co-precipitation of 140La into silica nanoparticles produced with the Stober method and radiolabeling of mesoporous silica nanoparticles in 0.1M HEPES at pH 7.5 and 80C for 1 hour both showed radiochemical yields of ~90%. Current studies are underway investigating the radiolabeling of silica nanoparticles with 225Ac alone and with the co-incorporation of 89Zr. Additionally, the retention of 225Ac’s daughter radionuclides will be investigated.

Silica nanoparticles as a vehicle for 225Ac/89Zr delivery for use as a theragnostic agent in targeted α-therapy

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.