Radiation Biology of EPR Oxygen Images

EPR 氧气图像的放射生物学

• 批准号: 8238838
• 负责人: HOWARD J HALPERN
• 金额: $ 27.33万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8238838
• 关键词: Adverse effects; Animal Model; Animals; Breast Carcinoma; Caliber; Carcinoma; Data; Dose; Effectiveness; Electron Spin Resonance Spectroscopy; Electrons; Elements; Failure; Funding; Grant; Human; Hypoxia; Image; Inbred C3H Mice; Intensity-Modulated Radiotherapy; Investigation; Literature; Magnetic Resonance Imaging; Malignant Neoplasms; Mammals; Measurement; Mus; Oryctolagus cuniculus; Oxygen; Probability; Property; Radiation; Radiation therapy; Radiobiology; Rattus; Relative (related person); Reporting; Resolution; Solid Neoplasm; Specific qualifier value; Techniques; Testing; Therapeutic; Treatment Efficacy; Validation; Vascular Endothelial Growth Factors; Work; base; cancer radiation therapy; efficacy testing; fibrosarcoma; improved; research study; statistics; tumor

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.

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、大鼠和兔子的动物肿瘤中定量的局部pO2分布。窄 EPR 谱线的氧展宽以 1-3 托分辨率报告每个 1mm3 图像体素中的 pO2。这项工作成功地展示了 1) 氧气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 (HF10) 的 EPROI 体素分数提供的信息，对 50% 肿瘤对照剂量进行独立的、统计上显着的锐化； 3)基于HF10的VEGF和EPROI的显着空间相关性； 4) 当治疗到控制所有 FSa 纤维肉瘤 50% (TCD50) 所需的剂量时，对于 HF10>8% 的肿瘤，控制率仅为 28%，而对于 HF10<8% 的肿瘤，控制率增加到 92%。在下一个资助周期中，我们建议探索 EPROI 作为 2 厘米大鼠 13762 例癌症 IMRT 剂量涂抹的基础，选择这些癌症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以下具体目标：探索 1) 在 TCD50 中添加固定剂量的有效性，该剂量针对基于 EPROI 的缺氧区域的 IMRT 增强，与向氧合良好的肿瘤区域添加相同的增强剂量相比。等体积 2) 增加缺氧区域的剂量，减少氧合良好区域的剂量。这将与统一 TCD50 的交付进行比较。 3) 向肿瘤区域添加与 HF10 成比例的分级剂量。这项工作将测试氧气成像在小型哺乳动物剂量绘制中的使用效果。它将提供提高放射治疗疗效并减少其副作用的途径。 公共健康相关性：这项工作继续研究一种新技术，以预测癌症放射治疗的治愈可能性，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，报告每 1 立方毫米体积的动物肿瘤中的氧气含量。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。