Table of Contents
International Journal of Molecular Imaging
Volume 2011, Article ID 694179, 6 pages
http://dx.doi.org/10.1155/2011/694179
Research Article

Autoradiographic Mapping of 5-HT1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

1Uppsala Imanet AB, GE Healthcare, P.O. Box 967, 751 09 Uppsala, Sweden
2Department of Clinical Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden
3AstraZeneca R&D, 151 85 Södertälje, Sweden
4Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Box 574, 75123 Uppsala, Sweden

Received 24 May 2011; Revised 11 August 2011; Accepted 12 August 2011

Academic Editor: Habib Zaidi

Copyright © 2011 Örjan Lindhe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist.