(-)-N-[11C]propyl-norapomorphine:: A positron-labeled dopamine agonist for PET imaging of D2 receptors
(-)-N-[11C]propyl-norapomorphine:: A positron-labeled dopamine agonist for PET imaging of D2 receptors
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DOI：
10.1016/s0969-8051(00)00144-x
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发表时间：
2000-08-01
影响因子：
3.1
通讯作者：
Laruelle, M
中科院分区：
文献类型：
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作者：
Hwang, DR;Kegeles, LS;Laruelle, M
用放射性标记的激动剂对神经受体进行成像，可能会提供有关感兴趣受体的激动剂亲和力状态的有价值的信息。我们报道了[C-11]标记的(-)-N-丙基-去甲吗啡[(-)-NPA]的放射合成、在啮齿类动物中的生物分布以及在狒狒体内的成像研究。(-)-[C-11]NPA是由去甲吗啡与[C-11]丙酰氯反应，再经氢化铝锂还原而成。[C-11]二氧化碳与乙基溴化镁反应，再与邻苯二甲酰氯反应，制得[C-11]丙酰氯。合成结束时(-)-[C-11]NPA的放化产率为2.5%，合成时间为60min。比活度为1700+/-1900mCi/mMol(N=7；EOS时为110-5200mCi/mMol)。啮齿动物体内分布研究表明，[C-11](-)-NPA在D-2受体丰富区摄取较高，注射后5min、30min和60min纹状体/小脑比值分别为1.7、3.4和4.4。注射氟哌啶醇(1 mg/kg)后30min，纹状体/小脑比值降至1.3，(-)-[C-11]NPA也通过狒狒正电子发射断层扫描(PET)进行评估。在对照条件下(N=4)，示踪剂快速摄取，注射后45min纹状体/小脑比值达到2.86±0.15。静脉注射氟哌啶醇(0.2 mg/kg)后，45min时纹状体/小脑比值为1.29，证明该新示踪剂与D-2受体存在特异性结合。据我们所知，目前在使用放射性标记的D-2激动剂的报道中，在狒狒身上发现的纹状体/小脑比率为2.8是最高的。(-)-[C-11]NPA是一种很有前途的新型D-2激动剂PET示踪剂，可用于体内D-2受体的PET探测。核医学生物27；6：533-539,2000。(C)2000 Elsevier Science Inc.保留所有权利。
Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [C-11]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[C-11]NPA was prepared by reacting norapomorphine with [C-11]propionyl chloride and a lithium aluminum hydride reduction. [C-11]Propionyl chloride was prepared by reacting [C-11]CO2 with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[C-11]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700 +/- 1900 mCi/mu mol (N = 7; ranged 110-5200 mCi/mu mol at EOS). Rodent biodistribution studies showed high uptake of [C-11](-)-NPA in D-2 receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3, (-)-[C-11]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions (N = 4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86 +/- 0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection, The result demonstrated the existence of specific binding of this new tracer to the D-2 receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D-2 agonist. (-)-[C-11]NPA is a promising new D-2 agonist PET tracer for probing D-2 receptors in vivo using PET. NUCL MED BIOL 27;6:533-539, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.