In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography.

In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11C-nomifensine was administered i.v. in trace amounts (10-50 micrograms) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the time-course of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo.