ArticleEJNMMI research2014
An evaluation of the brain distribution of [(11)C]GSK1034702, a muscarinic-1 (M 1) positive allosteric modulator in the living human brain using positron emission tomography.
Article in EJNMMI research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00937846 (An Open Label Positron Emission Tomography), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label Positron Emission Tomography (PET) Study to Investigate Brain Penetration by [Carbonyl-11C] GSK1034702 in Healthy Subjects
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 2-Mortality, Jarisch-Herxheimer reaction, impact on pregnancy.PLoS neglected tropical diseases · 2021Pooled it
- Louse-borne relapsing fever-A systematic review and analysis of the literature: Part 1-Epidemiology and diagnostic aspects.PLoS neglected tropical diseases · 2021Pooled it
- Muscarinic Receptor PET in Neurodegeneration: Promise, Pitfalls, and Translational Priorities.Medical sciences (Basel, Switzerland) · 2026Review
- PET in the characterization of immune diseases and development of therapeutics.Oxford open immunology · 2025Review
- Neuroimaging in psychedelic drug development: past, present, and future.Molecular psychiatry · 2023Review
- Imaging Cholinergic Receptors in the Brain by Positron Emission Tomography.Journal of medicinal chemistry · 2023Review
- PET as a Translational Tool in Drug Development for Neuroscience Compounds.Clinical pharmacology and therapeutics · 2022Review
- Update on PET Tracer Development for Muscarinic Acetylcholine Receptors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- First-in-Human Assessment ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- Article
- In Vitro Pharmacological Characterization and In Vivo Validation of LSN3172176 a Novel M1 Selective Muscarinic Receptor Agonist Tracer Molecule for Positron Emission Tomography.The Journal of pharmacology and experimental therapeutics · 2018Article
- Article
- Copper-Mediated Radiofluorination of Arylstannanes with [Organic letters · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe ability to quantify the capacity of a central nervous system (CNS) drug to cross the human blood-brain barrier (BBB) provides valuable information for de-risking drug development of new molecules. Here, we present a study, where a suitable positron emission tomography (PET) ligand was not available for the evaluation of a potent muscarinic acetylcholine receptor type-1 (M1) allosteric agonist (GSK1034702) in the primate and human brain. Hence, direct radiolabelling of the novel molecule was performed and PET measurements were obtained and combined with in vitro equilibrium dialysis assays to enable assessment of BBB transport and estimation of the free brain concentration of GSK1034702 in vivo.
methodsGSK1034702 was radiolabelled with (11)C, and the brain distribution of [(11)C]GSK1034702 was investigated in two anaesthetised baboons and four healthy male humans. In humans, PET scans were performed (following intravenous injection of [(11)C]GSK1034702) at baseline and after a single oral 5-mg dose of GSK1034702. The in vitro brain and plasma protein binding of GSK1034702 was determined across a range of species using equilibrium dialysis.
resultsThe distribution of [(11)C]GSK1034702 in the primate brain was homogenous and the whole brain partition coefficient (V T) was 3.97. In contrast, there was mild regional heterogeneity for GSK1034702 in the human brain. Human whole brain V T estimates (4.9) were in broad agreement with primate V T and the f P/f ND ratio (3.97 and 2.63, respectively), consistent with transport by passive diffusion across the BBB.
conclusionIn primate and human PET studies designed to evaluate the transport of a novel M1 allosteric agonist (GSK1034702) across the BBB, we have demonstrated good brain uptake and BBB passage consistent with passive diffusion or active influx. These studies discharged some of the perceived development risks for GSK1034702 and provided information to progress the molecule into the next stage of clinical development.
trial registrationClinical trial details: 'Brain Uptake of GSK1034702: a Positron Emission Tomography (PET) Scan Study.'; clinicaltrial.gov identifier: NCT00937846 .
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.