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

2-硝基咪唑类化合物是公认的低氧细胞放射增敏剂，已被应用于恶性肿瘤的放射治疗。这些化合物选择性地积累在低氧细胞中。在本研究中，我们在动物实验中使用了一种新的缺氧标志物-18&gt；F-FRP170来进行脑缺血的成像，它可能能够描绘即使在脑缺血的缺氧条件下仍然有效的半影区，并可以通过血运重建恢复。(材料和方法)选用雄性SD大鼠。用戊巴比妥钠腹腔注射麻醉大鼠。将尼龙线栓子插入左侧颈内动脉，导致大脑中动脉血流受阻。左侧大脑中动脉闭塞30min后，静脉注射74MBq的[18F]FRP170。阻断后210分钟注射0.185MBq的[14C]IAP作为血流标志物。麻醉…注射[14C]IAP后10s处死d只大鼠。大脑被迅速从头骨上取出并冷冻在干冰中。在冰冻切割机上切取20米厚的冠状切片。这些切片被放置在与通用成像板接触的位置。获得放射自显影图像。在缺血半球和非缺血半球的[14C]IAP图像上放置了15个感兴趣的正方形区域。我们使用示踪胶片将ROI放在与[18F]FRP170图像相同位置的其他图像上。每个感兴趣区的摄取值用放射自显影强度表示。得到了两种放射性药物的分布曲线，并进行了比较。(结果)[18F]FRP170摄取增加的区域与轻度至中度的灌注区相对应，也可在灌注区周围显示。我们估计这些区域是缺氧或半暗带区域。血流灌注区严重减少，摄取[18F]FRP170减少。我们估计这些区域是缺血核心区或梗死区。(结论)本文描述的方法使我们能够区分缺血中心和半影区。该制剂的临床应用将为决定是否应该进行血液循环重建或溶栓治疗提供有用的信息。然而，在该制剂可以用于临床之前，还需要进一步的研究。较少

(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