A PET study of [11C]β-CIT-FE binding to the dopamine transporter in the monkey and human brain

Several radiolabelled cocaine analogues have been proposed for brain imaging of the dopamine transporter in research on neuropsychiatric disorders and drug abuse. In a recent positron emission tomography (PET) study we labelled the cocaine analogue β-CIT-FE with carbon-11 and demonstrated high specific binding in the monkey striatum. In the present study, the selectivity of [11C]β-CIT-FE binding in the primate brain was examined by pretreatment experiments with reference ligands for the dopamine, serotonin and norepinephrine transporter. In three healthy human subjects the regional binding of [11C]β-CIT-FE was analysed using equilibrium and kinetic analyses. A Scatchard analysis showed that [11C]β-CIT-FE bound in a saturable manner yielded a density value of the same order as that reported in vitro. The pharmacological characterization indicated that a high degree of [11C]-CIT-FE binding in the primate striatum represents the dopamine transporter. In human subjects the radioligand provided high brain uptake and reached peak equilibrium within 1 hour after i.v. injection. Different quantitative approaches gave similar values for the binding potential. The results support the view that [11C]β-CIT-FE is a suitable radioligand for clinical studies of the dopamine transporter. In particular for studies requiring short data acquisition or repeated PET measurements on the same day.