通过单光子发射计算机断层扫描（SPECT）对家兔脑中与5-羟色胺转运体结合的[123I]ADAM进行体内定量分析。

Ye Xin-Xian, Hwang Jeng-Jong, Hsieh Jih-Fang, Chen Jyh-Cheng, Chou Yueh-Ting, Tu Kao-Yin, Wey Shiaw-Pyng, Ting Gann

Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC.

Nucl Med Biol. 2004 Nov;31(8):995-1003. doi: 10.1016/j.nucmedbio.2004.08.008.

BACKGROUND

A novel radioiodine ligand [(123)I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) has been suggested as a promising serotonin transporter (SERT) imaging agent for the central nervous system. In this study, the biodistribution of SERTs in the rabbit brain was investigated using [(123)I] ADAM and mapping images of the same animal produced by both single-photon emission computed tomography (SPECT) and microautoradiography. A semiquantification method was adopted to deduce the optimum time for SPECT imaging, whereas the input for a simple fully quantitative tracer kinetic model was provided from arterial blood sampling data.

METHODS

SPECT imaging was performed on female rabbits postinjection of 185 MBq [(123)I] ADAM. The time-activity curve obtained from the SPECT images was used to quantify the SERTs, for which the binding potential was calculated from the kinetic modeling of [(123)I] ADAM. The kinetic data were analyzed by the nonlinear least squares method. The effects of the selective serotonin reuptake inhibitors fluoxetine and p-chloroamphetamine (PCA) on rabbits were also evaluated. After scanning, the same animal was sacrificed and the brain was removed for microautoradiography. Regions-of-interest were analyzed using both SPECT and microautoradiography images. The SPECT images were coregistered manually with the corresponding microautoradiography images for comparative study.

RESULTS

During the time interval 90-100 min postinjection, the peak specific binding levels in different brain regions were compared and the brain stem was shown to have the highest activity. The target-to-background ratio was 1.89+/-0.02. Similar studies with fluoxetine and PCA showed a background level for SERT occupation. Microautoradiography demonstrated a higher level of anatomical details of the [(123)I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain.

CONCLUSION

SPECT imaging of the rabbit brain with [(123)I] ADAM showed high affinity, high specificity, and favorable kinetics. The time-activity curve showed that the accumulation of the [(123)I] ADAM in the brain stem reached a maximum between 90 and 100 min postinjection. The microautoradiography provides high-resolution images of the rabbit brain. Our results for the [(123)I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.

背景

一种新型放射性碘配体[（123）I]ADAM（2-（（2-（（二甲氨基）甲基）苯基）硫代）-5-碘苯胺）已被认为是一种有前景的用于中枢神经系统的5-羟色胺转运体（SERT）显像剂。在本研究中，使用[（123）I]ADAM研究了家兔脑中SERT的生物分布，并通过单光子发射计算机断层扫描（SPECT）和微放射自显影术生成了同一只动物的图谱图像。采用半定量方法推断SPECT显像的最佳时间，而简单的完全定量示踪剂动力学模型的输入则来自动脉血采样数据。

方法

对注射185 MBq[（123）I]ADAM后的雌性家兔进行SPECT显像。从SPECT图像获得的时间-活性曲线用于量化SERT，通过[（123）I]ADAM的动力学模型计算其结合潜能。动力学数据采用非线性最小二乘法进行分析。还评估了选择性5-羟色胺再摄取抑制剂氟西汀和对氯苯丙胺（PCA）对家兔的影响。扫描后，处死同一只动物并取出大脑进行微放射自显影。使用SPECT和微放射自显影图像分析感兴趣区域。将SPECT图像与相应的微放射自显影图像手动配准以进行对比研究。

结果

在注射后90 - 100分钟的时间间隔内，比较了不同脑区的峰值特异性结合水平，结果显示脑干的活性最高。靶本底比为1.89±0.02。用氟西汀和PCA进行的类似研究显示了SERT占据的本底水平。微放射自显影显示[（123）I]ADAM分布的解剖细节水平高于家兔脑的SPECT显像。

结论

用[（123）I]ADAM对家兔脑进行SPECT显像显示出高亲和力、高特异性和良好的动力学。时间-活性曲线显示，[（123）I]ADAM在脑干中的蓄积在注射后90至100分钟达到最大值。微放射自显影提供了家兔脑的高分辨率图像。我们关于[（123）I]ADAM在家兔脑中生物分布的结果表明，这种新的放射性配体适合作为SERT的选择性SPECT显像剂。