Radiation Biology of EPR Oxygen Images

描述（由申请方提供）：电子顺磁共振（EPR）氧成像（EPROI）提供了同基因小鼠、大鼠和兔动物肿瘤中的定量局部pO 2分布。窄EPR谱线的氧增宽以1-3 μ m的分辨率报告每个1 mm 3图像体素中的pO 2。这项工作已经成功地显示了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）50%肿瘤控制剂量的独立的、统计上显著的锐化，其中添加了由具有pO 2小于10 μ l（HF 10）的EPROI体素的分数提供的信息; 3）VEGF和基于EPROI的HF 10的显著空间相关性; 4）当治疗至控制所有FSa纤维肉瘤的50%（TCD 50）所需的剂量时，在HF 10>8%的肿瘤中控制仅为28%，而对于HF 10 <8%的肿瘤，控制增加至92%。在下一个资助周期中，我们建议探索EPROI作为2cm大鼠13762癌中IMRT剂量绘制的基础，选择该方法是为了通过增加尺寸来简化IMRT。我们为下一个资助周期提出了以下具体目标：探索以下措施的有效性：1）向TCD 50中增加固定剂量，靶向基于EPROI的缺氧区域的IMRT加强，与向等体积的氧合良好的肿瘤区域增加相同的加强剂量相比; 2）向缺氧区域增加剂量，向氧合良好的区域减少剂量。这将与递送均匀的TCD 50进行比较。3)向肿瘤区域添加与HF 10成比例的分级剂量。这项工作将测试在小型哺乳动物剂量绘画中使用氧成像的功效。它将为提高放射治疗效果和减少其副作用提供一条途径。 公共卫生相关性：这项工作继续研究一种新技术，以预测使用放射疗法治疗癌症的治愈可能性，并提高放射治疗癌症的治愈率。该技术涉及注射到动物体内的无毒化合物的非侵入性电子磁共振图像，其报告了动物肿瘤的每个1 mm 3体积中的氧气量。这最终将指导额外辐射剂量的放置，以增强人类肿瘤的辐射治疗。

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. PUBLIC HEALTH RELEVANCE: This work continues the investigation of a new technique to predict cure likelihood using radiation therapy for cancers and to improve the cure of cancers with radiation. The technique involves a non-invasive electron magnetic resonance image of a non-toxic compound, injected in an animal, which reports the amount of oxygen in each of the 1 mm3 volumes of the animal tumor. This eventually will guide the placement of extra radiation dose to enhance human tumor treatment with radiation.