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Departments of Psychiatry and Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
West Haven VA Medical Center, West Haven, Connecticut
Clinical Brain Disorders Branch, IRP, NIMH Neuroscience Center at St. Elizabeths, Washington, DC
Correspondence: For correspondence and reprints contact: Anissa Abi-Dargham, MD, Dept. of Psychiatry, Yale University and West Haven VA Medical Center/116A2, 950 Campbell Ave., West Haven, CT 06516.
ABSTRACT
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.
Key Words: SPECT • brain • benzodiazepine receptors • iodine-123-iomazenil
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