A NEW PET LIGAND FOR THE DOPAMINE TRANSPORTER - STUDIES IN THE HUMAN BRAIN

Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphen idate (ritalin), has been shown to bind uniquely to the dopamine trans porter in the baboon brain. This study characterizes its binding in th e human brain and measures its test-retest reproducibility. Methods: S tudies were done in seven normal controls, each of whom was scanned wi th [C-11]d-threo-methylphenidate on two different occasions. Six subje cts were scanned twice 3-5 wk apart without intervention to assess rep roducibility. One subject was scanned sequentially before and after tr eatment with methylphenidate to assess binding saturability. Graphical analysis was used to obtain tissue distribution volumes (DV). The rat io of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVB G/DVCB), which corresponds to (B-max/Kd) + 1 was used to estimate dopa mine transporter availability. Results: Highest tracer uptake occurred in the basal ganglia, where activity peaked 7-11 min postinjection. T he 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 ac tivity had cleared at 74 min. Time-activity curves for [C-11]d-threo-m ethylphenidate in the basal ganglia and cerebellum were highly reprodu cible. 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 reduc ed DVBG/DVCB by 62% and B-max/Kd by 91 %. Conclusion: These studies de monstrate that [C-11]d-threo-methylphenidate binding in the human brai n is reversible, highly reproducible and saturable. Thus, it is an app ropriate PET ligand to measure dopamine transporter availability.