Radiosynthesis of the candidate β-amyloid radioligand [11C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys
Version of Record online: 29 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 64, Issue 10, pages 733–741, October 2010
How to Cite
Andersson, J. D., Varnäs, K., Cselényi, Z., Gulyás, B., Wensbo, D., Finnema, S. J., Swahn, B.-M., Svensson, S., Nyberg, S., Farde, L. and Halldin, C. (2010), Radiosynthesis of the candidate β-amyloid radioligand [11C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys. Synapse, 64: 733–741. doi: 10.1002/syn.20782
- Issue online: 3 AUG 2010
- Version of Record online: 29 MAR 2010
- Manuscript Accepted: 12 JAN 2010
- Manuscript Received: 3 SEP 2009
- AstraZeneca Pharmaceuticals
- radioligand development;
- positron emission tomography;
- amyloid plaques;
- Alzheimer's disease
β-Amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Aβ-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [11C]AZD2184 ([11C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand. [11C]5 was prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert-butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [11C]methyl iodide followed by deprotection using water. Four brain PET measurements in two cynomolgus monkeys and one whole-body PET measurement were performed with [11C]5. There was a high and rapid brain uptake (2.2–3.4% of injected dose at 2 min). The distribution of brain radioactivity was fairly uniform, with early to late-brain concentration ratios (peak vs. 60 min) higher for [11C]5 than ratios previously reported for [11C]PIB (8.2 and 4.6, respectively). Based on the whole-body data, it was estimated that an effective dose in an adult male would be 6.2 μSv/MBq and thus would be safe from a radiation point of view for multiple scans within the same year. [11C]5 shows binding characteristics, suggesting low levels of white-matter retention, and may thus provide improved contrast when compared with currently used PET radioligands for visualization of Aβ-deposits. On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [11C]5 should be useful for routine clinical studies. Synapse 64:733–741, 2010. © 2010 Wiley-Liss, Inc.