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In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [ 11 C]WIN 35,428
Author(s) -
Wong Dean F.,
Yung Babington,
Dannals Robert F.,
Shaya Elias K.,
Ravert Hayden T.,
Chen Catherine A.,
Chan Boon,
Folio Traci,
Scheffel Ursula,
Ricaurte George A.,
Neumeyer John L.,
Wagner Henry N.,
Kuhar Michael J.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890150205
Subject(s) - dopamine , dopamine transporter , putamen , caudate nucleus , chemistry , radioligand , endocrinology , mazindol , medicine , striatum , dopamine plasma membrane transport proteins , pharmacology , receptor , dopaminergic
[ 11 C]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), [ 11 C]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 [ 11 C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D 2 dopamine receptors with [ 11 C]NMSP in the same MPTP‐treated animals showed much less reduction in the postsynaptic D 2 dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [ 11 C]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 (K 3 /K 4 ) 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 k 3 /k 4 ratio from 6.7 to 3.7, and 46% in the putamen k 3 /k 4 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 [ 11 C]WIN 35,428 alone. Taken together, these data indicate that [ 11 C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site. © 1993 Wiley‐Liss, Inc. This article is a US government work and as such, is in the public domain in the United States of America.