Volkow N D, Ding Y S, Fowler J S, Wang G J, Logan J, Gatley S J, Schlyer D J, Pappas N
Medical Department, Brookhaven National laboratory, Upton, NY 11973, USA.
J Nucl Med. 1995 Dec;36(12):2162-8.
Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphenidate (ritalin), has been shown to bind uniquely to the dopamine transporter in the baboon brain. This study characterizes its binding in the human brain and measures its test-retest reproducibility.
Studies were done in seven normal controls, each of whom was scanned with [11C]d-threomethylphenidate on two different occasions. Six subjects were scanned twice 3-5 wk apart without intervention to assess reproducibility. One subject was scanned sequentially before and after treatment with methylphenidate to assess binding saturability. Graphical analysis was used to obtain tissue distribution volumes (DV). The ratio of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVBG/DVCB), which corresponds to (Bmax/Kd) + 1 was used to estimate dopamine transporter availability.
Highest tracer uptake occurred in the basal ganglia, where activity peaked 7-11 min postinjection. The half-clearance time for the tracer in brain regions other than the basal ganglia was 74 min. In the basal ganglia, only 10%-15% of the activity had cleared at 74 min. Time-activity curves for [11C]d-threo-methylphenidate in the basal ganglia and cerebellum were highly reproducible. The average percent change for the absolute value for DVBG/DVCB was 6.5% +/- 4% (range 0-12%). Methylphenidate pretreatment decreased basal ganglia uptake but not cortical or cerebellar binding and reduced DVBG/DVCB by 62% and Bmax/Kd by 91%.
These studies demonstrate that [11C]d-threo-methylphenidate binding in the human brain is reversible, highly reproducible and saturable. Thus, it is an appropriate PET ligand to measure dopamine transporter availability.
碳-11-d-苏式甲基苯丙胺，即甲基苯丙胺（利他林）的活性对映体，已被证明能特异性地结合狒狒大脑中的多巴胺转运体。本研究对其在人脑中的结合特性进行了表征，并测量了其重测再现性。
对7名正常对照者进行了研究，每位对照者在两个不同时间点接受[11C]d-苏式甲基苯丙胺扫描。6名受试者在无干预的情况下，间隔3 - 5周进行两次扫描以评估再现性。1名受试者在接受甲基苯丙胺治疗前后进行了序贯扫描以评估结合饱和性。采用图形分析法获得组织分布容积（DV）。基底神经节（BG）与小脑（CB）的DV比值（DVBG/DVCB），相当于（Bmax/Kd） + 1，用于估计多巴胺转运体的可用性。
示踪剂摄取最高的部位是基底神经节，注射后7 - 11分钟活性达到峰值。基底神经节以外脑区的示踪剂半清除时间为74分钟。在基底神经节，74分钟时仅有10% - 15%的活性清除。基底神经节和小脑中[11C]d-苏式甲基苯丙胺的时间-活性曲线具有高度再现性。DVBG/DVCB绝对值的平均变化百分比为6.5% ± 4%（范围0 - 12%）。甲基苯丙胺预处理降低了基底神经节的摄取，但不影响皮质或小脑的结合，并使DVBG/DVCB降低62%，Bmax/Kd降低91%。
这些研究表明，[11C]d-苏式甲基苯丙胺在人脑中的结合是可逆的、高度可重复的且具有饱和性。因此，它是一种用于测量多巴胺转运体可用性的合适正电子发射断层扫描（PET）配体。
