INVIVO EVALUATION OF STRIATAL DOPAMINE REUPTAKE SITES USING C-11 NOMIFENSINE AND POSITRON EMISSION TOMOGRAPHY
INVIVO EVALUATION OF STRIATAL DOPAMINE REUPTAKE SITES USING C-11 NOMIFENSINE AND POSITRON EMISSION TOMOGRAPHY
复制标题
DOI：
10.1111/j.1600-0404.1987.tb03582.x
复制
发表时间：
1987-10-01
影响因子：
3.5
通讯作者：
LANGSTROM, B
中科院分区：
文献类型：
--
作者：
AQUILONIUS, SM;BERGSTROM, K;LANGSTROM, B
在体外，诺米芬辛对大脑中的多巴胺再摄取部位表现出高度的亲和力和特异性。在本研究中，静脉注射11C-诺米芬辛。微量(10-50微克)氯胺酮麻醉恒河猴(6-10公斤体重)用正电子发射断层扫描(PET)测量不同脑区放射性的时程变化。共进行6次基线实验，持续时间为60~80min。另一种再摄取抑制剂马吲哚(0.3 mg/kg)，地塞帕明(0.5 mg/kg)，静脉注射诺米芬新(2-6 mg/kg)后重复上述过程。或螺环酮(0.3 mg/kg静脉注射)在第二次注射11C-诺米芬辛之前。放射性摄取最高的是多巴胺支配的纹状体，最低的是含有小脑的区域，已知那里几乎没有多巴胺能神经元。注射诺米芬新和马吲哚后，纹状体和小脑摄取~(11)C-诺米芬辛衍生放射性的差异显着减小，而地昔帕明和螺环丙酮则不显着。这些结果表明，在活体内，纹状体摄取11C-Nomifensin，如用PET测量的那样，涉及与多巴胺再摄取部位的特异性结合。在人类首次在健康志愿者身上应用11C-诺米芬辛和PET时，区域放射性摄取与在恒河猴的基线实验中相似。健康受试者注射11C-诺米芬新50分钟后，纹状体/小脑比值为1.6。在一例偏侧帕金森病患者中，这一比率对侧为1.1，对患侧为1.3。~(11)C-诺米芬辛和正电子发射计算机断层扫描是活体测量人纹状体多巴胺能神经末梢的良好方法。
In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11C-nomifensine was administered i.v. in trace amounts (10-50 .mu.g) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the time-course of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11C-nomifensin, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the rejection of 11C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo.