Browsing by Author "Shrock, Zachary"

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    Enhancing Radiation Therapy Through Cherenkov Light-Activated Phototherapy.
    (International journal of radiation oncology, biology, physics, 2018-03) Yoon, Suk W; Tsvankin, Vadim; Shrock, Zachary; Meng, Boyu; Zhang, Xiaofeng; Dewhirst, Mark; Fecci, Peter; Adamson, Justus; Oldham, Mark
    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.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.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.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.
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    Modeling and Maximizing Cherenkov Emissions from Medical Linear Accelerators: A Monte Carlo Study
    (2017) Shrock, Zachary

    Purpose: Cherenkov light is a natural byproduct of MV radiotherapy; recent results demonstrate that it can activate the drug psoralen sufficiently to induce cytotoxicity and increase MHC1 signal in vitro. Here, we investigate Cherenkov radiation from common radiotherapy beams using Monte Carlo, as well as methods to maximize Cherenkov production per unit dose, using filters placed in the beam path.

    Methods: GAMOS, a GEANT4-based framework for Monte Carlo simulations, was used to model primary photon beams using spectra from a Varian linear accelerator and mono-energetic electron beams. Cherenkov photon spectra and track length along with dose were scored when irradiating a sphere of water with radius 50cm and SSD=50cm. Further measurements were taken with photon beams irradiating a 17.8cm3 cubic water phantom at 1mm3 detectors with depths of 8 to 9cm; SSD was set to 94cm. Finally, measurements were taken with filters of varying material and thickness placed 15cm below a 10MV FFF beam source.

    Results: Simulated Cherenkov spectra were found to have strong overlap with the psoralen absorbance spectrum; dose and Cherenkov photon track length measurements established that higher beam energies had greater Cherenkov production per unit dose, with 18MV providing greater Cherenkov/dose than 6MV by a factor of 4. Simulations with filters suggest that copper and iron filters increase Cherenkov per dose more than aluminum for a given filter thickness, but that aluminum yields a greater boost for a given dose rate.

    Conclusion: Initial work has been completed to show that the Cherenkov spectrum produced by radiotherapy beams is well suited for activation of psoralen, and that higher energy photon beams will result in more psoralen activation due to greater Cherenkov radiation per unit dose. We have also demonstrated that significant boosts in Cherenkov/dose can be achieved with the use of filters without overly compromising dose rate. Future work should expand analysis to include optical properties of tissues as well as additional filter materials.