Radiation Biology of EPR Oxygen Images

描述(由申请人提供)：已经开发出一种新的成像方法，用于成像活组织中的氧浓度。电子顺磁共振(EPR)成像(EPRI)得益于Nycomed Innovation(马尔莫，西南)公司开发的新型自旋探测器。这些探测器具有EPR谱，只有一条简单的单线，几乎比大多数以前可用的自旋探测器窄一个数量级。新的光谱建模算法允许从更强烈但失真的光谱中准确地提取光谱信息。通过静脉注射自旋探针，我们已经能够在20分钟内获得空间分辨率为0.6 mm、氧分辨率为3.5托的C3H小鼠腿部FSA肿瘤的氧气图像。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。尽管埃彭多夫电极测量的辐射固化能力与氧分压有很好的相关性，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低氧参数相关联。三个特定的目标将测试1)从EPRI氧气图像获得的摘要参数在多大程度上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TCD50定量相关，2)EPRI氧气图像与Oxylite PO2采样、单个肿瘤成对存活实验、彗星实验、匹莫硝唑滞留和缺氧蛋白的存在的相关性3)EPRI氧气图像区分不同氧合的小鼠肿瘤亚组的能力，以与整体TCD50治疗小鼠的不同小鼠存活相关。与其他低氧指标相关的研究已被设计为在空间上将测量结果与EPRI氧合图相关联，使用一种新的针头或套管针定位装置，用于肿瘤的成像夹具。这些研究将调查和验证这种非侵入性氧气成像技术，该技术提供了关于肿瘤和正常组织中氧气分布的丰富新信息。

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.