Radiation Biology of EPR Oxygen Images

描述(由申请人提供)：电子顺磁共振(EPR)氧气成像(EPROI)提供了同基因小鼠、大鼠和兔的动物肿瘤中PO2的定量定位分布。窄的EPR谱线的氧气展宽报告了在每1mm~3图像体素中具有1-3Torr分辨率的pO2。这项工作成功地证明了1)氧图像和点氧测量技术(Oxylite)之间的第一个共定位相关性；2)通过添加PO2小于10托的EPROI体素(HF10)提供的信息，50%的肿瘤控制剂量独立、统计上显著地锐化；3)VEGF和基于EPROI的HF10的显著空间相关性；4)当治疗到控制所有FSA纤维肉瘤的50%(TCD50)所需的剂量时，在HF10和GT；8%的肿瘤中，控制率仅为28%，而在HF10和HF10；8%的肿瘤中，控制率增加到92%。在下一个资金周期中，我们建议在2 cm大鼠13762个肿瘤中探索EproI作为调强放疗剂量画的基础，选择这些肿瘤是为了通过增大尺寸来简化调强放疗。我们为下一个资金周期提出了以下具体目标：1)在TCD50中添加固定剂量，靶向基于EPROI的缺氧区的IMRT增强，而不是将相同的增强剂量添加到相同体积的氧合良好的肿瘤区域；2)向缺氧区添加剂量，并减少对氧合良好的区域的剂量。这将与提供统一的TCD50进行比较。3)在与HF10成正比的肿瘤区域增加分级剂量。这项工作将测试氧气成像在小型哺乳动物剂量绘制中的效果。它将为提高放射治疗的疗效和减少其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.