氟化和碘化多巴胺制剂：用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）的D2成像剂。

Fluorinated and iodinated dopamine agents: D2 imaging agents for PET and SPECT.

作者信息

Chumpradit S, Kung M P, Billings J, Mach R, Kung H F

机构信息

Department of Radiology, University of Pennsylvania, Philadelphia 19104.

出版信息

J Med Chem. 1993 Jan 22;36(2):221-8. doi: 10.1021/jm00054a005.

DOI:10.1021/jm00054a005

PMID:8093734

Abstract

A novel series of dual-labeling D2 dopamine agents (labeled with either 18F or 123I for PET or SPECT imaging, respectively) was investigated. Two desired fluorinated and iodinated dopamine agents, FIDA1, (S)-(-)-2-(2-fluoroethoxy)-5-iodo-3-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]-benzamide, and FIDA2, (R)-(+)-2,3-dimethoxy-5-iodo-N-[(1-(4'-fluorobenzyl)-2- pyrrolidinyl)-methyl]benzamide, were synthesized. Both compounds displayed high affinity to the D2 receptor of rat striatal membrane preparations (Kd = 0.13 and 0.02 nM for FIDA1 and FIDA2, respectively). The biodistribution study in rats exhibited high localization in the striata of the brain with the striatum/cerebellum ratio reaching 29.3 and 13.1 at 1 h post iv injection for FIDA1 and FIDA2, respectively. Imaging studies with [18F]- and [123I]FIDA2 in monkeys, with PET and SPECT, respectively, showed comparable high selective striatal uptake. These results suggest that they are potentially useful D2 dopamine receptor imaging agents for PET and SPECT.

摘要

研究了一系列新型的双标记D2多巴胺剂（分别用18F或123I标记用于PET或SPECT成像）。合成了两种理想的氟化和碘化多巴胺剂，FIDA1，(S)-(-)-2-(2-氟乙氧基)-5-碘-3-甲氧基-N-[(1-乙基-2-吡咯烷基)甲基]-苯甲酰胺，和FIDA2，(R)-(+)-2,3-二甲氧基-5-碘-N-[(1-(4'-氟苄基)-2-吡咯烷基)-甲基]苯甲酰胺。两种化合物对大鼠纹状体膜制剂的D2受体均显示出高亲和力（FIDA1和FIDA2的Kd分别为0.13和0.02 nM）。在大鼠中的生物分布研究表明，在静脉注射后1小时，FIDA1和FIDA2在脑纹状体中的定位较高，纹状体/小脑比值分别达到29.3和13.1。分别用PET和SPECT对猴子进行的[18F]-和[123I]FIDA2成像研究显示，纹状体摄取具有相当高的选择性。这些结果表明，它们可能是用于PET和SPECT的有用的D2多巴胺受体成像剂。