Radiation Biology of EPR Oxygen Images

描述（由申请人提供）：开发了一种用于活体组织中氧浓度成像的新模式。电子顺磁共振（EPR）成像（EPRI）受益于Nyonut Innovations（马尔莫，SW）开发的新型自旋探针。这些探针具有EPR谱，具有简单的单线，并且比大多数先前可用的自旋探针窄近一个数量级。新的光谱建模算法允许从更强烈但失真的光谱中准确提取光谱信息。静脉注射自旋探针，我们已经能够从C3 H小鼠腿部的FSa肿瘤获得氧气图像，空间分辨率为0.6 mm，氧气分辨率为3.5 mm，在20分钟内获得。这项工作将测试这些氧气图像与辐射生物学的相关性。尽管通过Eppendorf电极测量的辐射可治愈性与pO 2相关的数据非常好，但任何测量氧气的新技术都必须与辐射效应和公认的放射生物学缺氧参数相关。三个具体目标将测试1）来自在经受人工氧合操作的小鼠中获得的EPRI氧图像的汇总参数与止血带诱导的缺氧、carbogen呼吸和carbogen呼吸加1 g/kg葡萄糖输注中的TCD 50定量相关的程度，2）EPRI氧图像与Oxylite pO 2采样、个体肿瘤配对存活测定、彗星测定、3）EPRI氧图像区分具有不同氧合的小鼠肿瘤中的亚组的能力，以与用总TCD 50处理的小鼠中的不同小鼠存活率相关。与其他缺氧测量相关的研究已被设计为使用新型针或套管针定位装置将测量与EPRI氧合图在空间上相关联，所述针或套管针定位装置将与其成像夹具中的肿瘤一起使用。这些研究将调查和验证这种无创氧成像技术，提供了丰富的新信息，有关肿瘤和正常组织中的氧分布。

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.