부산대학교 도서관

[C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high-affinity states of the D2 receptors (D2-high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [C]-(+)-PHNO and compare it with the well characterized antagonist D2 radioligand, [C]raclopride, in cat. [C]-(+)-PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 ± 0.85. Pre-treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011) antagonists indicated that [C]-(+)-PHNO binding in striatum is specific to D2 receptors. Within-subject comparisons showed that [C]-(+)-PHNO BP in striatum was almost 2.5-fold higher than that measured with [C]-(–)-NPA ([C]-(–)-N-propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [C]-(+)-PHNO was more sensitive to the dopamine releasing effect of amphetamine than [C]raclopride. Amphetamine induced up to 83 ± 4% inhibition of [C]-(+)-PHNO BP and only up to 56 ± 8% inhibition of [C]raclopride BP. Scatchard analyses of [C]-(+)-PHNO and [C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [C]-(+)-PHNO in brain, its high signal-to-noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [C]-(+)-PHNO has highly suitable characteristics for probing the D2-high with PET.