SPECT MEASUREMENT OF BENZODIAZEPINE RECEPTORS IN HUMAN BRAIN WITH IODINE-123-IOMAZENIL - KINETIC AND EQUILIBRIUM PARADIGMS

Iodine-123-iomazenil binding to benzodiazepine receptors in human brai n was measured with SPECT using kinetic and equilibrium methods. Metho ds: In the kinetic experiments (n = 6), regional time-activity curves after a single bo[us injection of the tracer were fit to a three-compa rtment model to provide estimates of the rate constants K-1 to k(4). T he binding potential (equal to the product of the receptor density and affinity) was derived from the rate constants. In the equilibrium met hod (n = 8), the tracer bolus injection was followed by a constant tra cer infusion to induce a sustained equilibrium state. The regional equ ilibrium volume of distribution was calculated as the ratio of the reg ional brain concentration-to-the free parent tracer steady-state plasm a concentration. In three experiments, a receptor-saturating dose of f lumazenil was injected for direct measurement of the nondisplaceable c ompartment distribution volume. Results: The kinetic and equilibrium m ethod results were in good agreement in all regions investigated. Iodi ne-125-iomazenil binding potential measured in vitro in 12 postmortem samples was found to be consistent with SPECT in vivo measurements. Co nclusion: These studies demonstrated the feasibility of quantification of receptor binding with SPECT.