title: Measurement of the proportion of D2 receptors configured in state of high affinity for agonists in vivo: a positron emission tomography study using [11C]N-propyl-norapomorphine and [11C]raclopride in baboons.
abstract: Dopamine D2 receptors are configured in interconvertible states of high (D(2 high)) or low (D(2 low)) affinity for agonists. The in vivo proportion of sites in high-affinity state remains poorly documented. Previous studies have established the D2 agonist [11C]N-propyl-norapomorphine (NPA) as a suitable positron emission tomography radiotracer for imaging D(2 high) in the living brain. To elucidate the proportion of D2 receptors configured in D(2 high) states in vivo, imaging studies were conducted in three baboons with both [11C]NPA and the D2 receptor antagonist [11C]raclopride. These studies were performed under noncarrier- and carrier-added conditions, to compare the Bmax of [11C]NPA and [11C]raclopride in the same animals. [11C]raclopride in vivo KD and Bmax were 1.59 +/- 0.28 nM (n = 3) and 27.3 +/- 3.9 nM (n = 3), respectively. The in vivo KD of [11C]NPA was 0.16 +/- 0.01 nM (n = 3), consistent with its affinity for D(2 high) reported in vitro. The maximal density of sites for [11C]NPA was 21.6 +/- 2.8 nM (n = 3), i.e., 79% of the [11C]raclopride Bmax. This result suggested that 79% of D2 receptors are configured as D(2 high) in vivo. This large proportion of D(2 high) sites might explain the vulnerability of D2 radiotracers to competition by endogenous dopamine, and is consistent with a previous report that the in vivo binding of agonist radiotracer [11C]NPA is more vulnerable to competition by endogenous dopamine than that of antagonist radiotracer [11C]raclopride.
authors: New York State Psychiatric Institute, 1051 Riverside Dr., Box #31, New York, NY 10032, USA. rn2012@columbia.edu
authors: Rajesh
authors: R
authors: Narendran
authors: Dah-Ren
authors: DR
authors: Hwang
authors: Mark
authors: M
authors: Slifstein
authors: Yuying
authors: Y
authors: Hwang
authors: Yiyun
authors: Y
authors: Huang
authors: Jesper
authors: J
authors: Ekelund
authors: Olivier
authors: O
authors: Guillin
authors: Erica
authors: E
authors: Scher
authors: Diana
authors: D
authors: Martinez
authors: Marc
authors: M
authors: Laruelle
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000378:metabolism*; D008297:Male; D010215:Papio; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis*
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; C009074:N-n-propylnorapomorphine; D001058:Apomorphine