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

使用新型 [18F] 标记的 2-硝基咪唑类似物 [18F]FRP170 进行脑缺血成像

• 批准号: 16591180
• 负责人: MARUOKA Shin
• 金额: $ 0.77万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591180/
• 关键词: 2-Nitroimidazole compounds; rat; cerebral ischemia; MCA occlusion

(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

（介绍）2-硝基咪唑类化合物是众所周知的缺氧细胞的放射敏感增敏剂，已被应用于恶性肿瘤的放疗。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一种新的缺氧标记物^<18 b> F-FRP170进行脑缺血成像，该标记物可以描述在脑缺血缺氧条件下仍然存在的半影区，并且可以通过血运重建来恢复。（材料与方法）本研究采用雄性SD大鼠。大鼠腹腔注射戊巴比妥钠麻醉。将尼龙线栓子插入左颈内动脉，阻断了大脑中动脉的血流。阻断左大脑中动脉30分钟后，静脉注射74MBq [18F]FRP170。闭塞后210分钟，注射0.185MBq [14C]IAP作为血流标志物。[14C]IAP注射开始10秒后，更多的大鼠被斩首。大脑被迅速从头骨中取出，并冷冻在干冰中。在低温切片机上切下20□m厚的冠状切片。切片与通用成像板接触。获得放射自显影图像。在[14C]IAP图像上放置了15个感兴趣的方形区域，覆盖了缺血半球和非缺血半球。我们使用跟踪胶片将roi放在与[18F]FRP170图像相同位置的另一张图像上。每个ROI的摄取值表示为放射自成像强度。得到了两种放射性药物的轮廓曲线并进行了比较。（结果）[18F]FRP170摄取增加的区域与灌注轻度至中度减少的区域相对应，也出现在灌注减少的区域周围。我们估计这些区域是缺氧或半影区。灌注区严重减少，[18F]FRP170摄取减少。我们估计这些区域是缺血核心或梗死区域。（结论）本文所描述的方法使我们能够区分缺血中心和半暗带。该药的临床应用将为确定是否应进行血液循环重建或溶栓治疗提供有用的信息。然而，在该药物用于临床之前，还需要进一步的研究。少