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In Vivo Mapping of Cholinergic Neurons in the Human Brain Using SPECT and IBVM

Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan

Correspondence: For correspondence or reprints contact: David E. Kuhl, MD, Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0028.

ABSTRACT

In the search for an in vivo marker of cholinergic neuronal integrity, we extended to human use the tracer (–)-5-[¹²³]iodobenzovesamicol (IBVM). Methods: IBVM, an analog of vesamicol that binds to the acetyicholine transporter on presynaptic vesicles, was prepared with specific activity greater than 1.11 x 10⁹ MBq mmole^–1. After intravenous injection of [¹²³I]IBVM, body distribution studies (n = 5) and brain SPECT studies (n = 5) were performed on normal human subjects (n = 10). SPECT images of the brain were collected sequentially over the first 4.5 hr following injection, and again 18 hr later. Data were realigned and transformed to stereotaxic coordinates, and localized activities were extracted for tracer kinetic analysis. The cerebral tracer input function was determined from metabolite-corrected radial arterial blood samples. The best data fit was obtained using a three-compartment model, including terms reflecting cerebral blood volume, exchange of free tracer between plasma and brain and specific binding. Results: Dissociation of bound tracer was negligible for up to 4 hr. For the fitted parameters reflecting transport (K₁) and binding site density index (k₃), coefficients of variation were approximately 8% in cortical regions of interest. Relative distributions corresponded well with post-mortem immunohistochemical values reported for the acetylcholine-synthesizing enzyme choline acetyltransferase, k₃ (IBVM binding site density index), and tracer activity distribution at 22 hr. but not at 4 hr after injection. Conclusion: SPECT imaging of [¹²³I]IBVM succeeds as an in vivo measure of cholinergic neuronal integrity and should be useful for the study of cerebral degenerative processes such as Alzheimer's disease.

Key Words: iodobenzovesamicol • cholinergic neurons • in vivo mapping of • SPECT

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