A new PET ligand for the dopamine transporter: studies in the human brain

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.