Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Neuroimage. 2011 Jan 1;54(1):123-30. doi: 10.1016/j.neuroimage.2010.08.010. Epub 2010 Aug 10.
The aim of this study was to visualize early infarction in the rat brain after ischemia using a translocator protein (TSPO) (18 kDa) PET ligand [(11)C]DAC with ultra-high specific activity (SA) of 3670-4450 GBq/μmol. An infarction model of rat brain was prepared by ischemic surgery and evaluated 2 days after ischemia using small-animal PET and in vitro autoradiography. Early infarction with a small increase of TSPO expression in the brain was visualized using PET with high SA [(11)C]DAC (average 4060 GBq/μmol), but was not distinguished clearly with usually reported SA [(11)C]DAC (37 GBq/μmol). Infarction in the rat brain 4 days after ischemia was visualized using high and usually reported SAs [(11)C]DAC. Displacement experiments with unlabeled TSPO-selective AC-5216 or PK11195 diminished the difference in radioactivity between ipsilateral and contralateral sides, confirming that the increased uptake on the infracted brain was specific to TSPO. In vitro autoradiography with high SA [(11)C]DAC showed that the TSPO expression increased on early infarction in the rat brain. High SA [(11)C]DAC is a useful and sensitive biomarker for the visualization of early infarction and the characterization of TSPO expression which was slightly elevated in the infarcted brain using PET.
本研究旨在使用超高比活度（SA）的 18 kDa 转位蛋白（TSPO）（11C）DAC 正电子发射断层扫描（PET）配体可视化缺血后大鼠脑内早期梗死。通过缺血手术制备大鼠脑梗死模型，并在缺血后 2 天使用小动物 PET 和体外放射自显影术进行评估。使用高 SA [11C]DAC（平均 4060GBq/μmol）进行 PET 可可视化具有 TSPO 表达小增加的早期梗死，但与通常报道的 SA [11C]DAC（37GBq/μmol）无法清楚地区分。在缺血后 4 天，使用高和通常报道的 SA [11C]DAC 可可视化大鼠脑梗死。未标记的 TSPO 选择性 AC-5216 或 PK11195 的置换实验减少了对侧和同侧之间放射性的差异，证实了梗死脑的摄取增加是 TSPO 的特异性。高 SA [11C]DAC 的体外放射自显影显示，在大鼠脑早期梗死中 TSPO 的表达增加。高 SA [11C]DAC 是一种有用且敏感的生物标志物，可用于可视化早期梗死和 TSPO 表达的特征，TSPO 表达在梗死脑内略有升高，可通过 PET 进行检测。
