HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noguchi, J. Articles by Senda, M. Search for Related Content PubMed PubMed Citation Articles by Noguchi, J. Articles by Senda, M.

Evaluation of Carbon-11-Labeled KF17837: A Potential CNS Adenosine A_2a Receptor Ligand

Positron Medical Center and Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Gerontology, Tokyo; Showa College of Pharmaceutical Sciences, Tokyo; Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo; Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Company, Shizuoka, Japan

Correspondence: For correspondence or reprints contact: Kiichi Ishiwata, PhD, Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi, Tokyo 173, Japan.

ABSTRACT

The ¹¹C-labeled KF17837 ([7-methyl-¹¹C](E)-8-(3,4-dimethoxystyryl)-1, 3-dipropyl-7-methylxanthine) was evaluated as a PET ligand for mapping adenosine A_2a receptors in the central nervous system (CNS). Methods: The regional brain distribution of [¹¹C]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [¹¹C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [¹¹C]KF17837 was performed by PET. Results: In mice, a high uptake of [¹¹C]KF17837 was found in the striatum in which A_2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A_2a antagonist CSC but not by nonxanthine-type A_2a antagonists ZM 241385 or SCH 58261, or an A_i antagonist KF15372. In the rat brain, [¹¹C]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. Conclusion: Carbon-11-KF17837 binds to adenosine A_2a receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A_2a antagonists.

Key Words: carbon-11-KF17837 • xanthine • adenosine A_2a receptor • central nervous system • PET

This article has been cited by other articles:

				T. Mihara, A. Noda, H. Arai, K. Mihara, A. Iwashita, Y. Murakami, T. Matsuya, S. Miyoshi, S. Nishimura, and N. Matsuoka Brain Adenosine A2A Receptor Occupancy by a Novel A1/A2A Receptor Antagonist, ASP5854, in Rhesus Monkeys: Relationship to Anticataleptic Effect J. Nucl. Med., July 1, 2008; 49(7): 1183 - 1188. [Abstract] [Full Text] [PDF]

				T. Nariai, Y. Shimada, K. Ishiwata, T. Nagaoka, J. Shimada, T. Kuroiwa, K.-I. Ono, K. Ohno, K. Hirakawa, and M. Senda PET Imaging of Adenosine A1 Receptors with 11C-MPDX as an Indicator of Severe Cerebral Ischemic Insult J. Nucl. Med., November 1, 2003; 44(11): 1839 - 1844. [Abstract] [Full Text] [PDF]