In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [¹¹C]WIN 35,428

[¹¹C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine transporter site by PET scanning in nonhuman primates and humans. In studies with a baboon (Papio anubis), [¹¹C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata. This accumulation was Partially blocked by prior administration of (−)cocaine (4 mg/kg, i.v. ). Placement of a unilateral lesion of dopamine‐containing nerve terminals with MPTP resulted in a unilateral reduction in [¹¹C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D₂ dopamine receptors with [¹¹C]NMSP in the same MPTP‐treated animals showed much less reduction in the postsynaptic D₂ dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [¹¹C]WIN 35,428. A total of ten normal human volunteers (five males and five females) with ages ranging from 19 to 81 years were studied. The caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min after injection of the tracer. Preliminary kinetic modeling with arterial plasma sampling resulted in an average binding potential (K₃/K₄) of 4.98 in the caudate nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol. Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90 min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k³/k⁴ ratio from 6.7 to 3.7, and 46% in the putamen k³/k⁴ from 4.7 to 2.5. Subject 8 had significant reductions of 20% in both the caudate/cerebellar ratio and the putamen/cerebellar ratio at 90 min. During the human PET studies, a number of neuropsychological tests and physiological measurements were performed. No significant changes were found after administration of the [¹¹C]WIN 35,428 alone. Taken together, these data indicate that [¹¹C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site. © 1993 Wiley‐Liss, Inc.