Enhancing Radiation Therapy through Cherenkov Light Activated Phototherapy
Menée sur une lignée cellulaire de mélanome et sur une lignée cellulaire de cancer mammaire d'origine murine, cette étude analyse l'intérêt d'utiliser l'effet Tcherenkov pour activer le psoralène, un photosensibilisant, et améliorer l'efficacité d'une radiothérapie
Purpose : This work investigates a new approach to enhance radiotherapy through a photo-therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam. The process is termed Radiotherapy Enhanced with Cherenkov photo-Activation (RECA). RECA is compatible with various photo-therapeutics, but here we focus on use with psoralen, an ultraviolet activated therapeutic with extensive history of application in superficial and extracorporeal settings. RECA has potential to extend the scope of psoralen treatments beyond superficial to deep seated lesions. Methods : In-vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT+RECA vs. RT alone for increasing cytotoxicity (local control) and increasing surface expression of Major Histocompatibility Complex Class I (MHC I). The latter represents potential for immune response amplification (increased antigen presentation), which has been observed in other psoralen therapies. Cytotoxicity assays included luminescence and clonogenics. MHC I assays were performed using flow cytometry. In addition, Cherenkov light intensity measurements were performed to investigate the possibility of increasing the Cherenkov light intensity per unit dose from clinical megavoltage beams, to maximize psoralen activation. Results : Luminescence assays showed that RECA treatment (2Gy at 6MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells respectively, compared to radiation and psoralen alone (i.e. Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA treated cells, compared to those receiving radiation and psoralen alone (∼450% and 250% at 3Gy and 6Gy respectively, p <<0.0001). Clonogenic assays of B16 cells at doses of 6Gy and 12Gy showed decreases in tumor cell viability of 7% (p=0.017) and 36% (p=0.006) respectively, when Cherenkov was present. Conclusion : This work demonstrates for the first time the potential for photo-activation of psoralen directly in-situ, from Cherenkov light generated by a clinical megavoltage treatment beam.