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Abstract
Cherenkov radiation (CR) derived from the decay of diagnostic and therapeutic radionuclides is currently being studied by the scientific community to determine if these emissions can be harnessed for cancer detection and therapy. While Cherenkov luminescence imaging (CLI) has been studied in the preclinical and clinical settings, Cherenkov radiation-induced cancer therapy (CRICT) is a relatively new area of research that harnesses the emitted photons to kill cancer cells through free radical generation and DNA damage. Nanoparticles seem well suited for developing a theranostic platform that would allow researchers to visualize therapy delivery and also generate the reactive oxygen species necessary to kill cancer cells. Herein, we report the preparation of an 89Zr-TiO2-MnO2 nanocomposite that incorporates transferrin onto the nanoparticle surface to enhance cancer cell growth inhibition. The incorporation of the positron emission tomography (PET) radioisotope 89Zr (half-life: 3.3 days) allowed for the detection of the nanoparticle using PET and for the creation of Cherenkov emissions that interacted with the nanoparticle surface to generate free radicals for therapy delivery. After preparation, these systems were observed to be stable in various media and provided excellent tumor growth control after being intratumorally injected into mice bearing CT-26 tumors. These results demonstrate that a therapeutically efficient CRICT platform can be generated using commercially available and affordable materials.

Affiliations

Pyeong Seok Choi 1, Jun Young Lee 1, Jung Ho Chae 1, Thaddeus Wadas 2, Zhen Cheng 3, Min Goo Hur 4, Jeong Hoon Park 1
1Accelerator Radioisotope Development Team, Korea Atomic Energy Research Institute, Jeongeup Si, Jeollabuk Do 56212, Republic of Korea.
2Department of Radiology, Carver College of Medicine, University of Iowa, 169 Newton Road, Iowa City, Iowa 52242, United States.
3State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
4Radiation Utilization and Facilities Management Division, Korea Atomic Energy Research Institute, Jeongeup Si, Jeollabuk Do 56212, Republic of Korea.