使用11C-ABP688对代谢型谷氨酸受体5进行的人体正电子发射断层扫描研究。

Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688.

作者信息

Ametamey Simon M, Treyer Valerie, Streffer Johannes, Wyss Matthias T, Schmidt Mark, Blagoev Milen, Hintermann Samuel, Auberson Yves, Gasparini Fabrizio, Fischer Uta C, Buck Alfred

机构信息

Center for Radiopharmaceutical Science of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, Zurich, Switzerland.

出版信息

J Nucl Med. 2007 Feb;48(2):247-52.

PMID:17268022

Abstract

UNLABELLED

3-(6-Methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime (11C-ABP688), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent.

METHODS

Six healthy male volunteers (mean age, 25 y; range, 21-33 y) were studied. Brain perfusion (15O-H2O) was measured immediately before each 11C-ABP688 PET scan. For anatomic coregistration, T1-weighted MRI was performed on each subject. Arterial blood samples for the determination of the arterial input curve were obtained at predefined time points, and 11C-ABP688 uptake was assessed quantitatively using a 2-tissue-compartment model.

RESULTS

An initial rapid uptake of radioactivity followed by a gradual clearance from all examined brain regions was observed. Relatively high radioactivity concentrations were observed in mGluR5-rich brain regions such as the anterior cingulate, medial temporal lobe, amygdala, caudate, and putamen, whereas radioactivity uptake in the cerebellum and white matter, regions known to contain low densities of mGluR5, was low. Specific distribution volume as an outcome measure of mGluR5 density in the various brain regions ranged from 5.45 +/- 1.47 (anterior cingulate) to 1.91 +/- 0.32 (cerebellum), and the rank order of the corresponding specific distribution volumes of 11C-ABP688 in cortical regions was temporal > frontal > occipital > parietal. The metabolism of 11C-ABP688 in plasma was rapid; at 60 min after injection, 25% +/- 0.03% of radioactivity measured in the plasma of healthy volunteers was intact parent compound.

CONCLUSION

The results of these studies indicate that 11C-ABP688 has suitable characteristics and is a promising PET ligand for imaging mGluR5 distribution in humans. Furthermore, it could be of great value for the selection of appropriate doses of clinically relevant candidate drugs that bind to mGluR5 and for PET studies of patients with psychiatric and neurologic disorders.

摘要

未标记

3 -（6 - 甲基 - 吡啶 - 2 - 基乙炔基） - 环己 - 2 - 烯酮 - O - 11C - 甲基肟（11C - ABP688），一种代谢型谷氨酸受体5（mGluR5）的非竞争性和高选择性拮抗剂，被评估作为正电子发射断层显像（PET）剂的潜力。

方法

研究了6名健康男性志愿者（平均年龄25岁；范围21 - 33岁）。在每次11C - ABP688 PET扫描前立即测量脑灌注（15O - H2O）。为进行解剖学配准，对每位受试者进行了T1加权磁共振成像（MRI）。在预定时间点采集动脉血样以测定动脉输入曲线，并使用双组织室模型定量评估11C - ABP688摄取。

结果

观察到放射性最初快速摄取，随后从所有检查的脑区逐渐清除。在富含mGluR5的脑区，如前扣带回、内侧颞叶、杏仁核、尾状核和壳核中观察到相对较高的放射性浓度，而在已知mGluR5密度低的小脑和白质区域，放射性摄取较低。作为各脑区mGluR5密度结果测量指标的特异性分布容积范围为5.45±1.47（前扣带回）至1.91±0.32（小脑），11C - ABP688在皮质区域相应的特异性分布容积的排序为颞叶＞额叶＞枕叶＞顶叶。11C - ABP688在血浆中的代谢很快；注射后60分钟，健康志愿者血浆中测得的放射性的25%±0.03%为完整的母体化合物。