Background/Objectives: Brain cancer is notoriously resistant to traditional treatments, including radiotherapy. Microbeam radiation therapy (MRT), arrays of ultra-fast synchrotron X-ray beams tens of micrometres wide (called peaks) and spaced hundreds of micrometres apart (valleys), is an effective alternative to conventional treatments. MRT’s advantage is that normal tissues can be spared from harm whilst maintaining tumour control. Combining MRT with targeted radiosensitisers, such as nanoparticles, chemotherapeutic drugs, and halogenated pyrimidine drugs, can further improve radiotherapy by enhancing radiation damage. However, the underlying mechanisms of MRT are still being understood, which is essential to ensuring the reliable and successful use of MRT.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.
背景/目的：脑癌对包括放射治疗在内的传统疗法具有显著的抵抗性。微束放射治疗（MRT）是一种由数十微米宽（称为峰值）且间隔数百微米（谷值）的超快同步加速器X射线束阵列组成的有效替代方案。MRT的优势在于能够在控制肿瘤的同时避免对正常组织造成伤害。将MRT与靶向放射增敏剂（如纳米颗粒、化疗药物和卤化嘧啶类药物）相结合，可通过增强辐射损伤进一步改善放疗效果。然而，MRT的潜在机制仍在探索中，这对于确保MRT可靠且成功的应用至关重要。 方法：通过γH2AX成像进行体外研究，并利用共聚焦显微镜和克隆形成细胞存活实验进行定量分析。 结果：研究表明，甲氨蝶呤化疗药物和碘脱氧尿苷能增强MRT的细胞杀伤效果，氧化铥纳米颗粒（TmNPs）可拓宽MRT峰值；通过γH2AX免疫荧光共聚焦显微镜定量DNA损伤，我们进一步深化了对MRT机制的理解。γH2AX图像验证了细胞生物学响应与MRT物理准直的一致性，并能够通过生物剂量学方法精确测量MRT微束特性。尽管此前研究认为具有挑战性，我们仍成功利用γH2AX成像生物测量法准确测定了表征MRT场的峰值-谷值剂量比（PVDR）。 结论：本研究首次实现了对含高原子序数放射增敏剂（包括纳米颗粒）的生物PVDR测量，并发现了若干新型放射增敏剂增强MRT的机制。这些结果深化了我们对放射增敏剂联合MRT治疗的理解，有助于推动该技术在未来癌症治疗中实现精准且成功的应用。
肿瘤(癌症)患者之家