TY - JOUR T1 - Receptor occupancy study of adenosine A2a receptor antagonists in conscious rhesus monkeys using positron emission tomography JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 61P LP - 61P VL - 48 IS - supplement 2 AU - Akihiro Noda AU - Yoshihiro Murakami AU - Takahiro Matsuya AU - Sosuke Miyoshi AU - Takuma Mihara AU - Nobuya Matsuoka AU - Shintaro Nishimura Y1 - 2007/05/01 UR - http://jnm.snmjournals.org/content/48/supplement_2/61P.3.abstract N2 - 204 Objectives: The present study was undertaken to measure adenosine A2a receptor (A2aR) occupancy of two A2aR antagonists (ASP7446, ASP5854) as candidates of antiparkinson agents in conscious rhesus monkeys to determine a promising candidate. Methods: ASP7446 (0.001−0.1 mg/kg) and ASP5854 (0.001−0.1 mg/kg) were tested using an A2aR specific radiotracer [11C]SCH442416 and a positron emission tomography (PET) in conscious rhesus monkeys. A2aR occupancy was measured at 1, 4, 8 hours after an intravenous single administration of each drug in three animals (4.4±1.5 yr, 5.25±1.44 kg). At each time point to measure A2aR occupancy, a dynamic PET scan for 40 min was performed following an intravenous bolus injection of the tracer for about 20 mCi. Binding potential (BP) of the tracer was estimated using a simplified reference tissue model (Lammertsma et al, 1996) in the striatum with the cerebellum as a reference region. A2aR occupancy was calculated as a binding potential (BP) reduction in the striatum. Results: Both drugs dose-dependently increased A2aR occupancy in the striatum and showed similar A2aR occupancy at 1h (estimated 80 % occupancy at 0.057 mg/kg [ASP7446], 0.041 mg/kg [ASP5854]), however, ASP5854 showed longer lasting occupancy that indicated longer exhibition of antiparkinson effect. Conclusions: The results showed two antiparkinson agents antagonized A2aR in the striatum and the duration that indicated effective period of the drug was also compared. Such pharmacodynamic study can directly reveal behavior of a drug in brain, thus it is useful for estimating an effective dose as well as selecting a promising drug candidate. ER -