1. PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
- Author
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Soheila Najafzadeh, Vanessa N. Barth, Yiyun Huang, Mika Naganawa, Nabeel Nabulsi, Antonio Navarro, Jim Ropchan, Ansel T. Hillmer, Richard E. Carson, Irina Esterlis, Kelly P. Cosgrove, Kelly Smart, Stephen R. Baldassarri, and Hong Gao
- Subjects
Adult ,Male ,medicine.medical_specialty ,Indoles ,Cognitive Neuroscience ,Scopolamine ,Striatum ,Receptors, Nicotinic ,Nicotine ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Piperidines ,Internal medicine ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,Chemistry ,Receptor, Muscarinic M1 ,Brain ,Muscarinic antagonist ,Human brain ,Middle Aged ,Macaca mulatta ,Acetylcholine ,Endocrinology ,medicine.anatomical_structure ,Nicotinic agonist ,Positron-Emission Tomography ,Cholinergic ,Original Article ,Female ,Radiopharmaceuticals ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n = 4) and nonhuman primates (n = 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n = 10) scanned with the α4β2* nicotinic ligand (−)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions, p = 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%, p
- Published
- 2021