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Analysis of Cherenkov Excitation in Tissue and the Feasibility of Cherenkov Excited Photodynamic Therapy

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S Saunders

Sara L Saunders1*, Adam K Glaser2 , Jacqueline M Andreozzi3 , Brian W Pogue4 , (1) Dartmouth College, Hanover, NH, (2) University of Washington, Seattle, WA, (3) Dartmouth College, Hanover, NH, (4) Dartmouth College, Hanover, NH


SU-F-T-684 (Sunday, July 31, 2016) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose: The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluence and radical oxygen species.

Methods: Simulations were completed using GAMOS/GEANT4 with a 6 MV photon beam in tissue. The effects of blood vessel diameter, blood oxygen saturation, and beam size were examined, recording spectral fluence. Experiments were carried out in solutions of photosensitizer and phantoms.

Results: Cherenkov produced by a 100x100um² 6 MV beam resulted in fluence of less than 1 nJ/cm²/Gy per 1 nm wavelength. At this microscopic level, differences in absorption of blood and water in the tissue affected the fluence spectrum, but variation in blood oxygenation had little effect. Light in tissue resulting from larger (10mm x10mm) 6 MV beams had greater fluence due to light transport and elastic scattering of optical photons, but this transport process also resulted in higher absorption shifts. Therefore, the spectrum produced by a microscopic beam was weighted more heavily in UV/blue wavelengths than the spectrum at the macroscopic level. At the macroscopic level, the total fluence available for absorption by Verteporfin (BPD) in tissue approached uJ/cm² for a high radiation dose, indicating that photodynamic activation seems unlikely. Tissue phantom confirmation of these light levels supported this observation, and photosensitization measurements with a radical oxygen species reporter are ongoing.

Conclusion: Simulations demonstrated that fluence produced by Cherenkov in tissue by 6 MV photon beams at typical radiotherapy doses appears insufficient to activate photosensitizers to the level required for threshold effects, yet this disagrees with published biological experiments. Experimental validation in tissue phantoms and cell studies are ongoing to clarify this discrepancy.

Funding Support, Disclosures, and Conflict of Interest: Funding from NIH grant R01CA109558.

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