Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
Nucl Med Biol. 2011 Aug;38(6):897-906. doi: 10.1016/j.nucmedbio.2011.01.009. Epub 2011 Mar 30.
A(2A) receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an (18)F-labeled A(2A) analog radiotracer ([(18)F]-MRS5425) for A(2A) receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A(2A) receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra.
[(18)F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D(2) agonist quinpirole (1.0 mg/kg) or D(2) antagonist raclopride (6.0 mg/kg).
Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres.
Thus, increase of A(2A) receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.
A(2A) 受体存在于基底神经节中，特别是在纹状体（尾壳核）的纹状苍白球 GABA 能神经元中。该脑区发生突触前多巴胺投射的变性和帕金森病中多巴胺的耗竭。我们使用正电子发射断层扫描 (PET) 开发了一种用于 A(2A) 受体成像的 (18)F 标记 A(2A) 类似物放射性示踪剂 ([(18)F]-MRS5425)。我们假设该示踪剂可对帕金森病大鼠模型中的 A(2A) 受体变化进行成像，该模型是通过将单胺能毒素 6-羟多巴胺 (6-OHDA) 单侧注射到黑质中来创建的。
在麻醉大鼠中静脉注射 [(18)F]-MRS5425，并收集 PET 成像数据。在正常大鼠和静脉注射生理盐水（基线）、D2 激动剂喹吡罗 (1.0 mg/kg) 或 D2 拮抗剂雷氯必利 (6.0 mg/kg) 后单侧 6-OHDA 损伤的大鼠中，在感兴趣区域测量纹状体中的放射性示踪剂注射剂量百分比 (%ID/g)。
基线 %ID/g 在 90 秒时达到最大值并保持 3.5 分钟的平台期，然后在此后缓慢下降。在 6-OHDA 损伤的大鼠中，与未损伤侧相比，损伤侧的 %ID/g 明显更高，并且与基线总 %ID/g（来自两个半球的数据合并）相比，从 4.5 分钟开始，直到 30 分钟采集结束时，喹吡罗刺激的总 %ID/g 明显更高。与基线或两个半球之间相比，雷氯必利没有引起摄取的任何变化。
因此，放射性 MRS5425 的 A(2A) 受体介导摄取的增加可能是帕金森成像的更好分子靶标。
