Purpose

Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[¹⁸F]fluoro-d-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice.

Procedures

The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with ^99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins.

Results

The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice.

Conclusions

Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.

中文翻译：

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在脑中风小鼠模型中使用梗塞狂热剂 2-Deoxy-2-[18F] 氟-D-葡糖二酸 (FGA) 对脑坏死进行 PET 检测。

目的

缺血性中风是世界范围内导致残疾的主要原因。受影响组织中坏死核心的体积在选择中风患者进行溶栓治疗或血管内血栓切除术中起着重要作用。在这项研究中，我们调查了最近报道正电子发射断层扫描（PET）剂2脱氧-2- [ ¹⁸ F]氟- d -glucaric酸（FGA），以确定在瞬时大脑中动脉闭塞模型坏死核心（吨-MCAO) 在小鼠中。

程序

的放射性药物，FGA，被控制的，快速的，和定量临床剂量的氧化合成的2-脱氧-2- [ ¹⁸ F]氟- d -葡萄糖（FDG），使用预制的试剂盒的一步反应。通过阻塞大脑中动脉 1 小时，在 CD-1 小鼠的左大脑半球诱导脑卒中，然后通过去除阻塞进行再灌注。发作后一天，使用^99m Tc 标记的六甲基丙烯胺肟 (HMPAO ) 进行灌注单光子发射断层扫描 (SPECT )，然后使用 FGA 进行 PET 采集。测定了血浆和脑组织匀浆的炎症和神经营养因子的标志物。

结果

基于试剂盒的合成能够在 5 分钟内将多达 2.2 GBq 的 FDG 转化为 FGA。PET 图像显示同侧半球的 F​​GA 积累比对侧半球多 375%。SPECT 图像显示同侧 HMPAO 积累减少到正常水平的 55%；FGA和HMAPO的同侧积累之间存在显着负相关（p  <0.05）。中风中 FGA 的积累也与同侧半球的 IL-6 水平相关。中风小鼠血浆中的 IL-6 或 TNFα 没有变化。

结论

FGA 的积累与灌注缺陷和炎症损伤密切相关。作为一种 PET 试剂，FGA 具有以高灵敏度、分辨率和特异性对脑卒中损伤中梗塞核心进行成像的潜力。