ArticleThe international journal of neuropsychopharmacology2018
Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia.
Article in The international journal of neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Cholinergic system in schizophrenia: A systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade.International journal of molecular sciences · 2022Pooled it
- Tryptophan challenge in individuals with schizophrenia and healthy controls: acute effects on circulating kynurenine and kynurenic acid, cognition and cerebral blood flow.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- "Pseudo-reference-based Input Function Shape" (pRef-IFS): Towards a True image-derived input function for PET kinetic modeling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- α7 nicotinic acetylcholine receptor, activated glia, and cognitive impairment in schizophrenia: a dual-tracer PET study.Molecular psychiatry · 2026Article
- Nicotinic acetylcholine receptors in pain modulation.Frontiers in pharmacology · 2026Review
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- Neuronal and Glial α7 Nicotinic Acetylcholine Receptors: Role in Alzheimer's Disease Pathophysiology.Life (Basel, Switzerland) · 2025Review
- Advances in PET Imaging of α7 Nicotinic Receptors: From Radioligand Development to CNS Applications.Basic & clinical pharmacology & toxicology · 2025Review
- Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic SV2A density in healthy rat brain: An in vivo microPET study.Psychophysiology · 2025Article
- Local depletion of large molecule drugs due to target binding in tissue interstitial space.CPT: pharmacometrics & systems pharmacology · 2024Review
- Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [Biological psychiatry · 2024Article
- Article
- Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig.Frontiers in neuroimaging · 2024Article
- Basal-Forebrain Cholinergic Nuclei Alterations are Associated With Medication and Cognitive Deficits Across the Schizophrenia Spectrum.Schizophrenia bulletin · 2023Article
- The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease.Nature reviews. Neurology · 2023Review
- Basal forebrain cholinergic signalling: development, connectivity and roles in cognition.Nature reviews. Neuroscience · 2023Review
- A Review of Potential Neuroimaging Biomarkers of Schizophrenia-Risk.Journal of psychiatry and brain science · 2023Article
- Development ofACS chemical neuroscience · 2022Article
- Relative Strengths of Three Linearizations of Receptor Availability: Saturation, Inhibition, and Occupancy Plots.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: The α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia. Study aims included: (1) confirmation of test-retest reproducibility of [18F]ASEM binding, (2) demonstration of specificity by competition with DMXB-A, an α7 nicotinic acetylcholine receptor partial agonist, (3) estimation of [18F]ASEM binding potentials and α7 nicotinic acetylcholine receptor density in vivo in humans, and (4) demonstrating the feasibility of studying α7 nicotinic acetylcholine receptor as a target for schizophrenia. Results: Test-retest PET confirmed reproducibility (>90%) (variability ≤7%) of [18F]ASEM volume of distribution (VT) estimates in healthy volunteers. Repeated sessions of PET in 5 healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of α7 nicotinic acetylcholine receptor by DMXB-A at 17% to 49% for plasma concentrations at 60 to 200 nM DMXB-A. In agreement with evidence postmortem, α7 nicotinic acetylcholine receptor density averaged 0.67 to 0.82 nM and inhibitor affinity constant averaged 170 to 385 nM. Median VT in a feasibility study of 6 patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus (P = 0.02, corrected for multiple comparions, Mann-Whitney test). Conclusions: The current results confirm the reproducibility of [18F]ASEM VT estimates and the specificity of the tracer for α7 nicotinic acetylcholine receptor. Preliminary findings from our feasibility study of [18F]ASEM binding in patients with schizophrenia are suggestive and provide guidance for future studies with more subjects.
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