Technical Note: On maximizing Cherenkov emissions from medical linear accelerators.

PURPOSE: Cherenkov light during MV radiotherapy has recently found imaging and therapeutic applications but is challenged by relatively low fluence. Our purpose is to investigate the feasibility of increasing Cherenkov light production during MV radiotherapy by increasing photon energy and applying specialized beam-hardening filtration. METHODS: GAMOS 5.0.0, a GEANT4-based framework for Monte Carlo simulations, was used to model standard clinical linear accelerator primary photon beams. The photon source was incident upon a 17.8 cm3 cubic water phantom with a 94 cm source to surface distance. Dose and Cherenkov production was determined at depths of 3-9 cm. Filtration was simulated 15 cm below the photon beam source. Filter materials included aluminum, iron, and copper with thicknesses of 2-20 cm. Histories used depended on the level of attenuation from the filter, ranging from 100 million to 2 billion. Comparing average dose per history also allowed for evaluation of dose-rate reduction for different filters. RESULTS: Overall, increasing photon beam energy is more effective at improving Cherenkov production per unit dose than is filtration, with a standard 18 MV beam yielding 3.3-4.0× more photons than 6 MV. Introducing an aluminum filter into an unfiltered 2400 cGy/min 10 MV beam increases the Cherenkov production by 1.6-1.7×, while maintaining a clinical dose rate of 300 cGy/min, compared to increases of ~1.5× for iron and copper. Aluminum was also more effective than the standard flattening filter, with the increase over the unfiltered beam being 1.4-1.5× (maintaining 600 cGy/min dose rate) vs 1.3-1.4× for the standard flattening filter. Applying a 10 cm aluminum filter to a standard 18 MV, photon beam increased the Cherenkov production per unit dose to 3.9-4.3× beyond that of 6 MV (vs 3.3-4.0× for 18 MV with no aluminum filter). CONCLUSIONS: Through a combination of increasing photon energy and applying specialized beam-hardening filtration, the amount of Cherenkov photons per unit radiotherapy dose can be increased substantially.

Enhancing Radiation Therapy Through Cherenkov Light-Activated Phototherapy.

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 AND MATERIALS: In vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT plus RECA versus RT alone for increasing cytotoxicity (local control) and increasing surface expression of major histocompatibility complex 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. The 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 (2 Gy at 6 MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells, respectively, compared with radiation and psoralen alone (ie, Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA-treated cells, compared with those receiving radiation and psoralen alone (approximately 450% and 250% at 3 Gy and 6 Gy, respectively, P << .0001). Clonogenic assays of B16 cells at doses of 6 Gy and 12 Gy showed decreases in tumor cell viability of 7% (P = .017) and 36% (P = .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.