SPECT QUANTIFICATION OF [I-123] IOMAZENIL BINDING TO BENZODIAZEPINE RECEPTORS IN NONHUMAN-PRIMATES .2. EQUILIBRIUM-ANALYSIS OF CONSTANT INFUSION EXPERIMENTS AND CORRELATION WITH IN-VITRO PARAMETERS

In vivo benzodiazepine receptor equilibrium dissociation constant, K-D, and maximum number of binding sites, B-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 [I-123]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 K-D (0.59 +/- 0.09 nM) and B-max (from 126 nM in the occipital region to 68 nM in the striatum). Two animals were killed and [I-125]iomazenil B-max and K-D were measured at 22 and 37 degrees C on occipital homogenate membranes. In vitro values of B-max (114 +/- 33 nM) and 37 degrees C K-D (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.