The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography
D. R. Weinberger, R. Gibson, R. Coppola, D. W. Jones, S. Molchan, T. Sunderland, K. F. Berman and R. C. Reba
Clinical Brain Disorders Branch, National Institute of Mental Health Neuroscience Center, St Elizabeths, Washington, DC 20032.
A high-affinity muscarinic receptor antagonist, 123IQNB
(3-quinuclidinyl-4-iodobenzilate 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 IQNB. 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.
