SPECT quantification of [ super(123)I]iomazenil binding to benzodiazepine receptors in nonhumans primates. II. Equilibrium analysis of constant infusion experiments and correlation with in vitro parameters

• Published in: Journal of cerebral blood flow and metabolism 1994-01, Vol.14 (3), p.453-465
• Main Authors: Laruelle, M, Abi-Dargham, A, Al-Tikriti, MS, Baldwin, R M, Zea-Ponce, Y, Zoghbi, S S, Charney, D S, Hoffer, P B, Innis, R B
• Format: Article
• Language: English
• Subjects: Papio anubis
• ISSN: 0271-678X

In vivo benzodiazepine receptor equilibrium dissociation constant, K sub(D), and maximum number of binding sites, B sub(max), 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 [ super(123)I]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. At the end of the experiments, a receptor saturating dose of flumazenil 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 K sub(D) and B sub(max). Two animals were killed and [ super(125)I]iomazenil B sub(max) and K sub(D) were measured at 22 and 37 degree C on occipital homogenate membranes. In vitro values of B sub(max) and 37 degree C K sub(D) 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.