2-(2-(二甲基氨基甲基)苯氧基)-5-碘苯胺：一种改进的5-羟色胺转运体显像剂。

2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent.

作者信息

Kung Hank F, Newman Suzanne, Choi Seok-Rye, Oya Shunichi, Hou Catherine, Zhuang Zhi-Ping, Acton Paul D, Plössl Karl, Winkler Jeffrey, Kung Mei-Ping

机构信息

Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

J Med Chem. 2004 Oct 7;47(21):5258-64. doi: 10.1021/jm049917p.

DOI:10.1021/jm049917p

PMID:15456270

Abstract

Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).

摘要

对血清素转运体（SERT）进行成像，是一种新兴的研究工具，可能有助于阐明药物作用机制以及监测抑郁症患者的治疗情况。我们制备了3, 2-(2-(二甲基氨基甲基)苯氧基)-5-碘苯胺（4）和2-(2-(二甲基氨基甲基)苄基)-5-碘苯胺（5）的两种新衍生物（对SERT的K(i)分别为0.37和48.6 nM）。[(125)I]4和[(125)I]5在大鼠脑中均表现出优异的摄取能力，且在下丘脑（60至240分钟之间）摄取量最高，而下丘脑是SERT密度最高的区域。[(125)I]4在下丘脑的特异性摄取在2小时时导致靶器官与非靶器官的比值（[下丘脑 - 小脑]/小脑）为4.3。[(125)I]4大鼠脑切片（2小时离体）的放射自显影显示出与已知SERT定位一致的优异区域分布模式。这些数据表明，[(123)I]4可能有助于通过单光子发射计算机断层扫描（SPECT）对脑中的SERT结合位点进行成像。