DOI: 10.1002/syn.20539. Positron emission tomography analysis of [<sup>11</sup>C]KW‐6002 binding to human and rat adenosine A<sub>2A</sub>receptors in the brain

Positron emission tomography analysis of [11C]KW‐6002 binding to human and rat adenosine A2Areceptors in the brain

10.1002/syn.20539

Crossref journal-article

Wiley

Synapse (311)

Abstract

AbstractAdenosine A2Areceptors are found on striatal neurones projecting to the external pallidum. KW‐6002 (istradefylline) is a potent and selective antagonist for the adenosine A2Areceptors in the CNS and acts to inhibit the excessive activity of this pathway in the MPTP marmoset model of PD, thus relieving parkinsonism. The objectives of this study were to investigate the regional binding of the novel positron emission tomography tracer [11C]KW‐6002 in the healthy human brain and the rat brain, along with receptor occupancy by cold KW‐6002 at varying doses in human. The highest [11C]KW‐6002 uptake in the rat brain was seen in striatum and lower levels in cortex and cerebellum. Brain [11C]KW‐6002 uptake was well characterized in humans by a two‐tissue compartmental model with a blood volume term, and the ED50of cold KW‐6002 was 0.5 mg in the striatum. Over 90% receptor occupancy was achieved with daily oral doses of greater than 5 mg. In humans, blockable binding was present in all gray matter structures including the cerebellum, which has not been reported to express A2Areceptors. MRS 1745, an A2Breceptor selective antagonist, had no effect on the cerebellar binding of [11C]KW‐6002 in rats, suggesting that this blockable signal is unlikely to result from an affinity for adenosine A2Breceptors. Synapse 62:671–681, 2008. © 2008 Wiley‐Liss, Inc.

Bibliography

Brooks, D. J., Doder, M., Osman, S., Luthra, S. K., Hirani, E., Hume, S., Kase, H., Kilborn, J., Martindill, S., & Mori, A. (2008). Positron emission tomography analysis of [11C]KWâ6002 binding to human and rat adenosine A2Areceptors in the brain. Synapse, 62(9), 671â681. Portico.

Authors 10

D.J. Brooks (first)
M. Doder (additional)
S. Osman (additional)
S.K. Luthra (additional)
E. Hirani (additional)
S. Hume (additional)
H. Kase (additional)
J. Kilborn (additional)
S. Martindill (additional)
A. Mori (additional)

References 52 Referenced 57

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Dates

Type	When
Created	17 years, 2 months ago (June 24, 2008, 1:53 p.m.)
Deposited	7 months ago (Jan. 30, 2025, 4:07 p.m.)
Indexed	7 months ago (Jan. 30, 2025, 4:40 p.m.)
Issued	17 years, 2 months ago (June 24, 2008)
Published	17 years, 2 months ago (June 24, 2008)
Published Online	17 years, 2 months ago (June 24, 2008)
Published Print	16 years, 11 months ago (Sept. 1, 2008)

Funders 0

None

BibTeX

@article{Brooks_2008, title={Positron emission tomography analysis of [11C]KW‐6002 binding to human and rat adenosine A2Areceptors in the brain}, volume={62}, ISSN={1098-2396}, url={http://dx.doi.org/10.1002/syn.20539}, DOI={10.1002/syn.20539}, number={9}, journal={Synapse}, publisher={Wiley}, author={Brooks, D.J. and Doder, M. and Osman, S. and Luthra, S.K. and Hirani, E. and Hume, S. and Kase, H. and Kilborn, J. and Martindill, S. and Mori, A.}, year={2008}, month=jun, pages={671–681} }

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