Abstract
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Objectives Photodynamic therapy (PDT) is limited to superficial and endoscope accessible lesions due to the shallow penetration of light in tissues and the reliance on tissue oxygenation to generate cytotoxic radicals. Our aim is to demonstrate the feasibility of using Cerenkov Radiation (CR) from clinical grade radionuclides such as 18FDG for depth-independent and highly selective CR induced therapy (CRIT) mediated by transferrin coated Titanium dioxide (TiO2-Tf) nanoparticles, a photocatalyst, for the treatment of diseases, with cancer as the primary focus of this study.
Methods We intravenously administered a one-time dose of TiO2-Tf (1 mg/kg body weight) and two doses of 18FDG (32.19 MBq/0.1 mL) within 72 h into separate mice (n=6) bearing fast growing HT1080 tumors, and monitored the animals over 45 days. Likewise, we also performed evaluation of CRIT on A549 lung cancer xenografts.
Results We observed that the tumor growth rate in mice undergoing CRIT was considerably lower than in untreated or control mice. Median survival increased from 15±2 d, for the untreated and control groups to 31 d for the TiO2-Tf+18FDG treated mice. We also observed attenuation of tumor growth and a significant increase in median survival to 22 d when mice were treated with a lower dose of 18FDG (15.91 MBq/0.1 mL) than described above. However, administration of tracer amounts of 18FDG (5.18 MBq/0.1 mL activity) did not induce CRIT, allowing us to distinguish the therapeutic dose for CRIT from the diagnostic dose of 18FDG, which was used to track treatment response and showed a much lower standard uptake value compared to untreated tumors.
Conclusions These initial results demonstrate the feasibility of developing a new strategy to treat cancer by CRIT, independent of cancer type. Lack of significant lesions in the liver and kidneys following CRIT indicates that CRIT is more effective in proliferating tumor cells than healthy tissues and that there is minimal off-target toxicity.