Imaging Cerebral Ischemia, Using a New [18F]-Labeled 2-Nitroimidazole Analog, [18F]FRP170

2-硝基咪唑类化合物是已知的乏氧细胞放射增敏剂，已被应用于恶性肿瘤的放射治疗。这些化合物选择性地在缺氧细胞中积累。在本研究中，我们在动物实验中使用新的缺氧标记物^F-FRP 170进行脑缺血成像<18>，该标记物可以描绘即使在脑缺血的缺氧条件下仍然存活的半暗带区域，并且可以通过血管重建来恢复。（材料与方法）雄性SD大鼠。通过腹腔注射戊巴比妥钠麻醉大鼠。将尼龙线栓子插入左颈内动脉导致大脑中动脉血流受阻。在左侧大脑中动脉闭塞后30分钟，静脉注射74 MBq的[18F] FRP 170。在闭塞后210分钟，注射0.185MBq的[14 C]IAP作为血流标记物。麻醉 ...更多信息 d大鼠在[14 C]IAP注射开始后10秒断头。大脑被迅速从头骨中取出，并在干冰中冷冻。在低温恒温切片机上切下20 μ m厚的冠状切片。将切片与通用成像板接触。获得放射自显影图像。将15个方形感兴趣区域放置在[14 C]IAP图像上，遍及缺血半球和非缺血半球。我们使用跟踪胶片将ROI放置在与[18F] FRP 170图像相同的位置的另一个图像上。每个ROI中的摄取值表示为放射自显影强度。得到了两种放射性药物的轮廓曲线并进行了比较。（结果）[18F] FRP 170摄取增加的区域与灌注轻度至中度减少的区域相对应，在灌注减少的区域周围也有分布。我们估计这些区域是缺氧或半影区。显示灌注面积严重减少，[18 F] FRP 170摄取减少。我们估计这些区域是缺血核心或梗死区域。（结论）该方法可区分缺血中心区和半暗带区。该制剂的临床应用将为临床上决定是进行血液循环重建还是溶栓治疗提供有用的信息。然而，在这种药物可以用于临床之前，还需要进一步的研究。少

(Introduction) 2-Nitroimidazole compounds are well-known radiosensitive sensitizers of hypoxic cells, and they have been applied to radiotherapy for malignant tumors. These compounds accumulate selectively in hypoxic cells. In the present study, we performed imaging of cerebral ischemia in animal experiments using a new hypoxic marker, ^<18>F-FRP170, which may enable depiction of the penumbra region that is still viable even under hypoxic conditions in cerebral ischemia and can be recovered by revascularization. (Materials and Methods) Male SD rats were used in this study. Rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Inserted nylon thread embolus into the left internal carotid artery resulted in blocking blood flow into the middle cerebral artery. 30 minutes after left middle cerebral artery occlusion, 74MBq of [18F]FRP170 was injected intravenously. At 210 minutes post-occlusion, 0.185MBq of [14C]IAP was injected as a blood flow marker. Anesthetize … More d rats were decapitated 10 seconds after the start of the [14C]IAP injection. The brains were removed rapidly from the skull and frozen in dry ice. 20□m thick coronal sections were cut on a cryostat microtome. The sections were placed in contact with general-use imaging plates. The autoradiographic images were obtained. 15 square regions of interest were placed on the [14C]IAP image throughout the ischemic hemisphere and nonischemic hemisphere. We put the ROIs on the other image at the same sites as the [18F]FRP170 image using the traced film. The uptake values in each ROI were expressed as the autoradiographic intensities. Profile curves of two radiopharmaceuticals were obtained and compared. (Results) The increased uptake areas of [18F]FRP170 were correspondent to slightly to moderately decreased perfusion areas, were also shown around decreased perfusion areas. We estimated those areas to be the regions of hypoxia or penumbra. Severely decreased perfusion areas with decreased uptake of [18F]FRP170 were shown. We estimated those areas to be the regions of ischemic core or infarction. (Conclusion) The method described here allowed us to differentiate between the ischemic center and the penumbra. Clinical application of this agent will provide useful information for determining whether reconstruction of the blood circulation or thrombolytic therapy should be applied. However, further studies are required before this agent can be used clinically. Less