Volkow N D, Fowler J S, Logan J, Gatley S J, Dewey S L, MacGregor R R, Schlyer D J, Pappas N, King P, wang G J
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
J Nucl Med. 1995 Jul;36(7):1289-97.
We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites.
PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV).
At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub-pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine.
At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter.
我们利用正电子发射断层扫描（PET）和示踪剂量的[11C]可卡因，在狒狒体内对大脑中可卡因与多巴胺转运体上的高亲和力位点的结合情况进行了表征。然而，示踪剂（亚药理）剂量的可卡因的结合模式，可能与以行为活性剂量服用该药物时观察到的模式不同，特别是因为体外研究表明，可卡因也与低亲和力结合位点结合。
使用PET比较和表征低亚药理剂量（平均剂量18微克）和药理剂量（8000微克）下[11C]可卡因在狒狒大脑中的结合情况。在同一天对同一只狒狒进行系列研究，以评估重复测量的可重复性，并评估抑制多巴胺、去甲肾上腺素和5-羟色胺转运体的药物的作用。利用大脑的时间-活性曲线和动脉血浆输入函数来计算稳态分布容积（DV）。
在亚药理剂量下，[11C]可卡因在纹状体中的结合更高，清除更慢，高于其他脑区。在药理剂量下，[11C]可卡因的分布更均匀。亚药理[11C]可卡因的Bmax/Kd对应于0.5 - 0.6，药理[11C]可卡因的Bmax/Kd对应于0.1 - 0.2。两点Scatchard分析得出Bmax = 2300皮摩尔/克，Kd' = 3600纳摩尔。亚药理剂量的[11C]可卡因的Bmax/Kd被可卡因和抑制多巴胺转运体的药物降低至0.1 - 0.2，但未被抑制5-羟色胺或去甲肾上腺素转运体的药物降低。这些药物均未改变药理剂量的[11C]可卡因的Bmax/Kd。
在亚药理剂量下，[11C]可卡因主要与多巴胺转运体上的高亲和力位点结合。
