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 brain was measured with SPECT using kinetic and equilibrium methods. Methods: In the kinetic experiments (n = 6), regional time-activity curves after a single bolus injection of the tracer were fit to a three-compartment model to provide estimates of the rate constants K₁ to k₄. The binding potential (equal to the product of the receptor density and affinity) was derived from the rate constants. In the equilibrium method (n = 8), the tracer bolus injection was followed by a constant tracer infusion to induce a sustained equilibrium state. The regional equilibrium volume of distribution was calculated as the ratio of the regional brain concentration-to-the free parent tracer steady-state plasma concentration. In three experiments, a receptor-saturating dose of flumazenil was injected for direct measurement of the nondisplaceable compartment distribution volume. Results: The kinetic and equilibrium method results were in good agreement in all regions investigated. Iodine-125-iomazenil binding potential measured in vitro in 12 postmortem samples was found to be consistent with SPECT in vivo measurements. Conclusion: These studies demonstrated the feasibility of quantification of receptor binding with SPECT.