Visualization of the dopamine transporter in the human brain postmortem with the new selective ligand [125I]PE2I

Using a new, 125I-labeled, selective high affinity dopamine transporter ligand, N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methy lph enyl)nort ropane (PE2I), the distribution of the dopamine transporter was characterized in the normal postmortem human brain using whole hemisphere autoradiography. PE2I was radioiodinated to high specific radioactivity (2200 Ci/mmol, 81 GBq/micromol). PE2I binds to the dopamine transporter with high potency and, in contrast to beta-CIT, it has very low affinities for the serotonin and noradrenaline transporters. The autoradiograms showed very intense binding in basal ganglia (putamen, nucleus caudatus, nucleus accumbens) and lower binding in substantia nigra. Very low or no binding was found in other brain structures, including the neocortex or cerebellum. The labeling of human dopamine transporters with [125I]PE2I was inhibited by the dopamine transporter inhibitors GBR 12909 and beta-CIT, but not by citalopram (serotonin transporter inhibitor) or maprotiline (noradrenaline transporter inhibitor). Possibly due to the relatively high lipophilicity of the compound (theoretical log p = 4.68), it accumulated slightly in white matter. Thus, in vitro autoradiography using [125I]PE2I provided detailed qualitative and quantitative evidence that the dopamine transporter is almost exclusively localized in the basal ganglia of the human brain. Moreover, the autoradiograms indicate that [11C]PE2I and [123I]PE2I should be suitable for the in vivo visualization of the human dopamine transporter with PET or SPECT, respectively.