Radiation Biology of EPR Oxygen Images

描述（由申请人提供）：电子顺磁共振（EPR）氧图像（EPROI）提供了同基因小鼠、大鼠和兔子动物肿瘤中pO2的定量定位分布。窄EPR谱线的氧展宽报告了pO2在每1mm3图像体素中的1-3 torr分辨率。这项工作已经成功地证明了1)氧图像和氧点测量技术（Oxylite）之间的第一个共定位相关性；2)随着pO2小于10 torr （HF10）的EPROI体素比例提供的信息的加入，50%肿瘤控制剂量的独立的、有统计学意义的锐化；3)基于VEGF和EPROI的HF10具有显著的空间相关性；4)当治疗剂量达到控制所有FSa纤维肉瘤50% （TCD50）所需的剂量时，HF10≤8%的肿瘤控制率仅为28%，而HF10<8%的肿瘤控制率为92%。在下一个融资周期中，我们建议探索EPROI作为2cm大鼠13762癌的IMRT剂量涂绘的基础，选择EPROI是为了便于通过增大尺寸进行IMRT。我们为下一个资助周期提出以下具体目标：探索1)向基于EPROI的缺氧区域添加固定剂量的TCD50靶向IMRT增强的有效性，与向同等体积的良好氧合肿瘤区域添加相同的增强剂量相比2)向缺氧区域添加剂量并向良好氧合区域添加减少剂量。这将与统一的TCD50的交付进行比较。3)在肿瘤部位按HF10成比例增加分级剂量。这项工作将测试氧成像在小型哺乳动物剂量绘画中的应用效果。这将为提高放射治疗的疗效和减少放射治疗的副作用提供一条途径。

DESCRIPTION (provided by applicant): Electron Paramagnetic Resonance (EPR) Oxygen Images (EPROI) provide quantitative localized pO2 distributions in animal tumors of syngeneic mice, rats, and rabbits. The oxygen broadening of narrow EPR spectral lines reports the pO2 with 1-3 torr resolution in each 1mm3 image voxel. This work has successfully shown 1) the first co-localized correlation between an oxygen image and a point oxygen measurement technique (Oxylite); 2) independent, statistically significant sharpening of the 50% tumor control dose with the addition of the information provided by the fraction of EPROI voxels with pO2 less than 10 torr (HF10); 3) significant spatial correlation of VEGF and EPROI based HF10; 4) when treated to the dose necessary to control 50% (TCD50) of all FSa fibrosarcomas, control is only 28% in tumors with HF10>8% while it increases to 92% for those with HF10<8%. In the next funding cycle we propose to explore EPROI as the basis for IMRT dose painting in 2cm rat 13762 carcinomas, chosen for ease of IMRT via increased size. We propose the following specific aims for the next funding cycle: exploring the effectiveness of 1) Adding a fixed dose to the TCD50 targeting an IMRT boost to an EPROI based hypoxic region, compared with adding the same boost dose to a well oxygenated tumor region of equal volume 2) Adding dose to the hypoxic region and reduced dose to a well oxygenated region. This would be compared with delivery of uniform TCD50. 3) Adding a graded dose to regions of the tumor proportional to the HF10. This work will test the efficacy of the use of oxygen imaging in dose painting in small mammals. It will provide a path to enhancement of radiation therapy efficacy and reduction of its side effects.