Radiation Biology of EPR Oxygen Images

描述（由申请人提供）：已经开发了一种新的方式来成像活组织中的氧浓度。电子顺磁共振（EPR）成像（EPRI）得益于Nycomed Innovations （Malmo， SW）开发的新型自旋探针。这些探针的EPR光谱有一条简单的单线，比以前可用的大多数自旋探针窄了近一个数量级。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，我们能够在20分钟内获得C3H小鼠腿部FSa肿瘤的氧图像，空间分辨率为0.6 mm，氧分辨率为3.5 torr。这项拨款的工作将测试这些氧气图像与辐射生物学的相关性。尽管Eppendorf电极测量的pO2与辐射固化率有很好的相关数据，但任何测量氧气的新技术都必须与辐射效应和已建立的放射生物学缺氧参数相关联。三个特定的目的将测试1)从接受人工氧合操作的小鼠中获得的EPRI氧图像的总结参数与止血带诱导缺氧，碳呼吸和碳呼吸加1 g/kg葡萄糖输注时tcd50的定量相关性的程度；2)EPRI氧图像与Oxylite pO2采样，个体肿瘤配对生存试验，彗星试验的相关性。3) EPRI氧图像区分不同氧合小鼠肿瘤亚群的能力与TCD50处理小鼠不同小鼠存活率的相关性。与其他缺氧测量相关的研究被设计成与EPRI氧合图在空间上相关，使用一种新型的针或套管定位装置与肿瘤在其成像装置中一起使用。这些研究将调查和验证这种无创氧成像技术，为肿瘤和正常组织中的氧分布提供丰富的新信息。

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.