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A Novel Method to Enhance Standard of Care Radiation Therapy: Cherenkov Light Activated Psoralen (CLAP)

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S Yoon

S Yoon1*, V Tsvankin1 , Z Shrock2 , B Meng2 , M Dewhirst1 , P Fecci1 , J Adamson1 , M Oldham1, (1) Duke University Medical Center, Durham, North Carolina, (2) Duke University, Durham, North Carolina

Presentations

SU-K-FS2-5 (Sunday, July 30, 2017) 4:00 PM - 6:00 PM Room: Four Seasons 2


Purpose: This work investigates the feasibility of a new approach to drive the efficacy of radiation therapy by increasing both local control and any systemic anti-cancer immune response. The approach is termed Cherenkov Light Activated Psoralen (CLAP), where Cherenkov light (CL) produced during radiation therapy (RT) is used to activate a phototherapeutic drug, psoralen, inside the tumor.

Methods: The in-vitro effect of CLAP was investigated in two murine cancer cell lines, breast 4T1 and melanoma B16. Cells were cultured on transparent plates with light transmission >90% down to 300nm. The plates were irradiated 0-6Gy from below so that all cells receive equal radiation dose. A thin (250μm) light block was placed underneath half of the plate, such that half the cells were exposed to CL and the other half were not. Cell Viability and surface MHC I assays were performed 48 hours after irradiation to investigate CLAP potential for increased local and systemic effects, respectively.

Results: CLAP increased cytotoxicity and surface Major Histocompatibility Complex I (MHC I) above and beyond radiation alone. CLAP reduced luminescence cell viability by 20% and 9.5% (p<0.001) for 4T1 and B16 cells respectively. Higher surface MHC I expression was observed for B16 cells treated with CLAP versus standard RT. The CL-induced MHC I increase was statistically significant only when psoralen was present (p<0.00025). The apparent success of CLAP in-vitro is attributed to high overlap between psoralen absorption and Cherenkov emission spectra. Cherenkov per dose enhancement of 13% is demonstrated using a low-Z filter, suggesting CL optimization potential by clinical beam manipulation.

Conclusion: The long-term potential of CLAP includes simple low-cost clinical translation, preservation of the benefits of state of the art radiation treatments, and addition of a novel phototherapeutic component, with potential to amplify any systemic response through immunogenic stimulation.


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