利用定量放射自显影技术对大鼠和小鼠脑中123I-ADAM结合位点的表征及其与5-羟色胺转运体的关系

Characterization of the binding sites for 123I-ADAM and the relationship to the serotonin transporter in rat and mouse brains using quantitative autoradiography.

作者信息

Lin Kun-Ju, Yen Tzu-Chen, Wey Shiaw-Pyng, Hwang Jeng-Jong, Ye Xin-Xian, Tzen Kai-Yuan, Fu Ying-Kai, Chen Jin-Chung

机构信息

Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan, Taiwan.

出版信息

J Nucl Med. 2004 Apr;45(4):673-81.

PMID:15073265

Abstract

UNLABELLED

Imaging of serotonin transporter (SERT) in the central nervous system may provide an important tool to evaluate some psychiatric disorders. Recently, a novel (123)I-labeled radiotracer, 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ((123)I-ADAM), has been developed that exhibited a high selectivity for SERT. The aim of this study was to characterize the biodistribution and specificity of (123)I-ADAM to SERT using quantitative autoradiography in both control and neurotoxin-treated animals.

METHODS

(123)I-ADAM (74 MBq) was injected intravenously into the mice to access its biodistribution in the brain via quantitative autoradiography. Further, rats with serotonin depleted by intraperitoneal injection of p-chloroamphetamine (PCA) were used to evaluate the specificity of (123)I-ADAM to SERT. The levels of biogenic amines were then measured and correlated with quantitative (123)I-ADAM labeling in control and PCA-treated rat brains.

RESULTS

The autoradiographic results showed that (123)I-ADAM accumulated in SERT-rich brain areas after systemic injection, including the globus pallidus, thalamus, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala, and raphe nucleus. The dorsal raphe nucleus had the highest initial uptake with a peak specific binding ratio (i.e., [target - cerebellum]/cerebellum) at 120 min after injection. (123)I-ADAM uptake was dramatically decreased in the hippocampus, thalamus, amygdala, geniculate nuclei, hypothalamus, raphe nucleus, and substantia nigra in PCA-lesioned rats. The decrement in radioactivity was more prominent at higher dosages of PCA and was in parallel with the changes in amounts of serotonin and 5-hydroxyindoleacetic acid in the prefrontal cortex.

CONCLUSION

This study demonstrates that regional distribution of (123)I-ADAM radioactivity is similar to the SERT localization in both rat and mouse brains. We also validated that destruction on central serotonergic neurons after PCA treatment inhibits the uptake of (123)I-ADAM in serotonin-rich brain regions. High specific binding to SERT in vivo makes (123)I-ADAM an appropriate radiotracer for solitary studies of serotonin functions in living humans.

摘要

未标记

对中枢神经系统中血清素转运体（SERT）进行成像可能为评估某些精神疾病提供重要工具。最近，一种新型的（123）I标记放射性示踪剂，2-((2-((二甲氨基)甲基)苯基)硫代)-5-碘苯胺（（123）I-ADAM）已被开发出来，它对SERT表现出高选择性。本研究的目的是在对照动物和经神经毒素处理的动物中，使用定量放射自显影法来表征（123）I-ADAM对SERT的生物分布和特异性。

方法

将（123）I-ADAM（74 MBq）静脉注射到小鼠体内，通过定量放射自显影法观察其在脑中的生物分布。此外，使用腹腔注射对氯苯丙胺（PCA）使血清素耗竭的大鼠来评估（123）I-ADAM对SERT的特异性。然后测量生物胺水平，并将其与对照大鼠和PCA处理大鼠脑中的定量（123）I-ADAM标记进行关联。

结果

放射自显影结果显示，全身注射后（123）I-ADAM在富含SERT的脑区蓄积，包括苍白球、丘脑、下丘脑、黑质、脚间核、杏仁核和中缝核。注射后120分钟时，中缝背核的初始摄取最高，特异性结合率峰值（即[靶区 - 小脑]/小脑）最高。在PCA损伤的大鼠中，海马、丘脑、杏仁核、膝状体核、下丘脑、中缝核和黑质中的（123）I-ADAM摄取显著降低。放射性的减少在较高剂量的PCA时更为明显，并且与前额叶皮质中血清素和5-羟吲哚乙酸含量的变化平行。

结论

本研究表明，（123）I-ADAM放射性的区域分布与大鼠和小鼠脑中的SERT定位相似。我们还证实，PCA处理后中枢5-羟色胺能神经元的破坏会抑制富含血清素的脑区对（123）I-ADAM的摄取。在体内对SERT的高特异性结合使得（123）I-ADAM成为在活体人类中单独研究血清素功能的合适放射性示踪剂。