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The Distribution of Cerebral Muscarinic Acetylcholine Receptors In Vivo in Patients With DementiaA Controlled Study With 123IQNB and Single Photon Emission Computed Tomography
Daniel R. Weinberger, MD;
Raymond Gibson, PhD;
Richard Coppola, DSc;
Douglas W. Jones, PhD;
Susan Molchan, MD;
Trey Sunderland, MD;
Karen Faith Berman, MD;
Richard C. Reba, MD
Arch Neurol. 1991;48(2):169-176.
Abstract
• A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-io-dobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IONB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.
Author Affiliations
From the Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health Neuroscience Center at St Elizabeths (Drs Weinberger, Coppola, Jones, and Berman), the Department of Nuclear Medicine, George Washington University (Drs Gibson and Reba), and the Unit on Geriatric Psychopharmacology, Laboratory of Clinical Science, National Institute of Mental Health (Drs Molchan and Sunderland), Washington, DC.
Footnotes
Accepted for publication August 1, 1990.
Reprint requests to Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health Neuroscience Center at St Elizabeths, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 (Dr Weinberger).
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