Biological properties of 2′-[18F]fluoroflumazenil for central benzodiazepine receptor imaging
Biological properties of 2′-[18F]fluoroflumazenil for central benzodiazepine receptor imaging
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DOI：
10.1016/j.nucmedbio.2004.12.004
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Lee, MC
中科院分区：
文献类型：
--
作者：
Chang, YS;Jeong, JM;Lee, MC
2 '-[F-18] fluoromazenil（8-fluoro-5-methyl-6-oxo-5，6-dihydro-4 H-benzo-[f]imidazo [1，5-a][1，4]diazepine-3-carboxylate，FFMZ）是一种新型的正电子发射剂，可用于苯并二氮卓类药物的显像。在本研究中，[F-18]FFMZ的生物学特性进行了研究。进行了人和大鼠血清中[18 F]FFMZ的稳定性试验。在小鼠中研究了生物分布，并从大鼠中获得了脑的磷光图像。使用大鼠脑（皮质和小脑的混合物）匀浆进行受体结合试验。从正常人类志愿者获得静态正电子发射断层扫描（PET）图像。虽然[F-18]FFMZ在人血清中稳定，但在大鼠血清中迅速水解。在10、30和60 min时，水解率分别为39%、63%和92%。根据小鼠的生物分布研究，在大多数器官中观察到略微均匀的分布（在2 - 3% ID/g之间）。由于胆汁排泄，肠摄取在1 h时增加至6% ID/g。1 h时，骨摄取从1.5%缓慢增加至3.5% ID/g。在大鼠的磷显像研究中观察到皮质、丘脑和小脑的高摄取，这可以被冷FMZ的共注射完全阻断。通过Scatchard作图法测定大鼠脑组织的Kd值和B-max，结果分别为1.45 +/- 0.26 nM和1.08 +/- 0.03 pmol/mg蛋白。正常人志愿者的PET图像显示以下递减顺序的高摄取：额叶皮质、颞叶皮质、枕叶皮质、小脑、顶叶皮质和丘脑。总之，新的FMZ衍生物，[F-18]FFMZ似乎是一个很有前途的PET剂的中央苯二氮卓类受体成像与方便的标记程序和特异性结合的属性。(c)2005年爱思唯尔公司All rights reserved.
A novel positron emitting agent, 2'-[F-18]fluoroflumazenil (fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate, FFMZ), has been reported for benzodiazepine imaging. In the present study, biological properties of [F-18]FFMZ were investigated. Stability tests of [18F]FFMZ in human and rat sera were performed. Biodistribution was investigated in mice and phosphorimages of brains were obtained from rats. A receptor binding assay was performed using rat brain (mixture of cortex and cerebellum) homogenate. A static positron emission tomography (PET) image was obtained from a normal human volunteer. Although [F-18]FFMZ was stable in human serum, it was rapidly hydrolyzed in rat serum. The hydrolysis was 39%, 63% and 92% at 10, 30 and 60 min, respectively. According to the biodistribution study in mice, somewhat even distribution (between 2 similar to 3% ID/g) was observed in most organs. Intestinal uptake increased up to 6% ID/g at 1 h due to biliary excretion. Bone uptake slowly increased from 1.5% to 3.5% ID/g at 1 h. High uptakes in the cortex, thalamus and cerebellum, which could be completely blocked by coinjection of cold FMZ, were observed by phosphorimaging study using rats. Determination of K-d value and B-max using rat brain tissue was performed by Scatchard plotting and found 1.45 +/- 0.26 nM and 1.08 +/- 0.03 pmol/mg protein, respectively. The PET image of the normal human Volunteer showed high uptake in the following decreasing order: frontal cortex, temporal cortex, occipital cortex, cerebellum, parietal cortex and thalamus. In conclusion, the new FMZ derivative, [F-18]FFMZ appears to be a promising PET agent for central benzodiazepine receptor imaging with a convenient labeling procedure and a specific binding property. (c) 2005 Elsevier Inc. All rights reserved.