Session: Radiotherapeutics: From Isotope Production to Targeted Radiotherapy:

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 studies with mesoporous nanoparticles show ~90% labeling for both ²²⁵Ac and ⁸⁹Zr. The retention of ²²⁵Ac’s daughter nuclei will be investigated with and without a thin layer of gold added to the nanoparticles. Additionally, incorporating ²²⁵Ac and ⁸⁹Zr via co-precipitation with the Stöber method is being investigated.

Tara Mastren

The University of Utah

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