title: SPECT quantification of [123I]iomazenil binding to benzodiazepine receptors in nonhuman primates: II. Equilibrium analysis of constant infusion experiments and correlation with in vitro parameters.
abstract: In vivo benzodiazepine receptor equilibrium dissociation constant, KD, and maximum number of binding sites, Bmax, were measured by single photon emission computerized tomography (SPECT) in three baboons. Animals were injected with a bolus followed by a constant i.v. infusion of the high affinity benzodiazepine ligand [123I]iomazenil. Plasma steady-state concentration and receptor-ligand equilibrium were reached within 2 and 3 h, respectively, and were sustained for the duration (4-9 h) of the experiments (n = 15). At the end of the experiments, a receptor saturating dose of flumazenil (0.2 mg/kg) was injected to measure nondisplaceable activity. Experiments were carried out at various levels of specific activity, and Scatchard analysis was performed for derivation of the KD (0.59 +/- 0.09 nM) and Bmax (from 126 nM in the occipital region to 68 nM in the striatum). Two animals were killed and [125I]iomazenil Bmax and KD were measured at 22 and 37 degrees C on occipital homogenate membranes. In vitro values of Bmax (114 +/- 33 nM) and 37 degrees C KD (0.66 +/- 0.16 nM) were in good agreement with in vivo values measured by SPECT. This study demonstrates that SPECT can be used to quantify central neuroreceptors density and affinity.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516.
authors.forename: M
authors.initials: M
authors.lastname: Laruelle
authors.forename: A
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: M S
authors.initials: MS
authors.lastname: al-Tikriti
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Y
authors.initials: Y
authors.lastname: Zea-Ponce
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000818:Animals; D001769:Blood / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism; D006706:Homeostasis; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D010215:Papio; D011963:Receptors, GABA-A / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil