Radiation Biology of EPR Oxygen Images

描述（由申请人提供）：已经开发出一种用于对活体组织中的氧浓度进行成像的新方式。电子顺磁共振 (EPR) 成像 (EPRI) 受益于 Nycomed Innovations（马尔默，瑞士）开发的新型自旋探针。这些探针的 EPR 光谱具有简单的单线，并且比大多数以前可用的自旋探针窄近一个数量级。新的光谱建模算法可以从更强烈但扭曲的光谱中准确提取光谱信息。注射自旋探针 iv，我们能够从 C3H 小鼠腿部的 FSa 肿瘤中获得氧气图像，空间分辨率为 0.6 毫米，氧气分辨率为 3.5 托，在 20 分钟内获得。这项资助的工作将测试这些氧气图像与辐射生物学的相关性。尽管有很好的数据将辐射固化性与通过 Eppendorf 电极测量的 pO2 相关联，但任何测量氧气的新技术都必须与辐射效应和完善的放射生物学低氧参数相关联。三个具体目标将测试 1) 在接受人工氧合操作的小鼠中获得的 EPRI 氧气图像的汇总参数与止血带引起的缺氧、卡本呼吸和卡本呼吸加 1 g/kg 葡萄糖输注中的 TCD50 定量相关的程度，2) EPRI 氧气图像与 Oxylite pO2 采样、个体肿瘤配对生存测定、彗星测定、哌莫硝唑保留和缺氧蛋白的存在的相关性 3) EPRI 氧图像能够区分具有不同氧合的小鼠肿瘤亚组，从而与接受总体 TCD50 治疗的小鼠中不同的小鼠存活率相关。与其他缺氧测量相关的研究旨在将测量结果与 EPRI 氧合图在空间上关联起来，使用一种新颖的针或套管针定位装置与成像夹具中的肿瘤一起使用。这些研究将调查并验证这种无创氧成像技术，该技术提供了有关肿瘤和正常组织中氧分布的大量新信息。

DESCRIPTION (provided by applicant): A new modality has been developed for imaging oxygen concentrations in living tissue. Electron Paramagnetic Resonance (EPR) Imaging (EPRI) has benefited by the development of novel spin probes by Nycomed Innovations (Malmo, SW). These probes have EPR spectra have a simple single line and that are nearly an order of magnitude narrower than most previously available spin probes. New spectral modeling algorithms allow the accurate extraction of spectral information from more intense, but distorted spectra. Injecting the spin probes iv, we have been able to derive oxygen images from FSa tumors in the legs of C3H mice with spatial resolution of 0.6 mm and oxygen resolution of 3.5 torr, obtained in 20 minutes. This work of this grant will test the relevance of these oxygen images to radiation biology. Despite the excellent data correlating radiation curability with pO2 as measured by Eppendorf electrodes, any new technique to measure oxygen must be correlated with radiation effect and well-established radiobiologic hypoxic parameters. Three specific aims will test 1) the extent to which summary parameters from EPRI oxygen images obtained in mice subject to artificial oxygenation manipulation quantitatively correlate with TCD50s in tourniquet induced hypoxia, carbogen breathing and carbogen breathing plus 1 g/kg glucose infusion, 2) the correlation of the EPRI oxygen image with Oxylite pO2 sampling, individual tumor paired survival assay, the comet assay, pimonidazole retention and the presence of hypoxia proteins 3) the ability of the EPRI oxygen image to distinguish subgroups among mouse tumors with different oxygenation to correlate with different mouse survival in mice treated to an overall TCD50. The studies correlating with other measures of hypoxia have been designed to spatially correlate the measurements with EPRI oxygenation maps, using a novel needle or trochar locating device to be used with the tumor in its imaging jig. These studies will investigate and validate this noninvasive oxygen imaging technology that provides a wealth of new information concerning oxygen distributions in tumors and normal tissues.