Striatal adenosine A_2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [¹⁸F]-MRS5425

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• 作者：Abesh Kumar Bhattacharjee^a ; Lixin Lang^a ; Orit Jacobson^a ; Bidhan Shinkre^b ; Ying Ma^a ; Gang Niu^a ; ^c ; William C. Trenkle^b ; Kenneth A. Jacobson^d ; Xiaoyuan Chen^a ; Dale O. Kiesewetter^a ; ^{dk7k@nih.gov"" rel=""nofollow}
• 关键词：SCH442416 ; MRS5425 ; Parkinson's disease ; Adenosine A_2A ; 6-OHDA ; rat
• 刊名：Nuclear Medicine and Biology
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：38
• 期：6
• 页码：897-906
• 全文大小：560 K

文摘

Introduction

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 ¹⁸F-labeled A_2A analog radiotracer ([¹⁸F]-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.

Methods

[¹⁸F]-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), D₂ agonist quinpirole (1.0 mg/kg) or D₂ antagonist raclopride (6.0 mg/kg).

Results

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.

Conclusion

Thus, increase of A_2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.