Microbeam Radiation Therapy Bio-Dosimetry Enhanced by Novel Radiosensitiser Combinations in the Treatment of Brain Cancer

新型放射增敏剂组合增强微束放射治疗生物剂量在脑癌治疗中的应用

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作者:Michael Valceski, Elette Engels, Sarah Vogel, Jason Paino, Dylan Potter, Carolyn Hollis, Abass Khochaiche, Micah Barnes, Alice O'Keefe, Matthew Cameron, Kiarn Roughley, Anatoly Rosenfeld, Michael Lerch, Stéphanie Corde, Moeava Tehei

Conclusions

The measurement of biological PVDR has been performed for the first time with high-Z radiosensitisers, including nanoparticles, and several novel radiosensitiser-enhanced MRT mechanisms were discovered. Our results deepen our understanding of MRT with radiosensitisers, and can contribute to its accurate and future successful use in treating cancer.

Methods

An in vitro study was performed using γH2AX imaging, and quantification was performed via confocal microscopy and a clonogenic cell survival assay.

Results

We show that methotrexate chemotherapeutics and iododeoxyuridine enhance MRT cell-killing and thulium oxide nanoparticles (TmNPs) broaden MRT peaks, and using γH2AX immunofluorescent confocal microscopy to quantify DNA damage, we further our knowledge of MRT mechanisms. γH2AX images verify the biological responses of cells aligning with the physical collimation of MRT, and we can accurately measure MRT microbeam characteristics bio-dosimetrically. The peak-to-valley dose ratio (PVDR), the ratio of the peak dose to the valley dose that characterises an MRT field, was accurately measured biologically using γH2AX imaging, despite studies previously finding this challenging. Conclusions: The measurement of biological PVDR has been performed for the first time with high-Z radiosensitisers, including nanoparticles, and several novel radiosensitiser-enhanced MRT mechanisms were discovered. Our results deepen our understanding of MRT with radiosensitisers, and can contribute to its accurate and future successful use in treating cancer.

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