ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2013
Determination of the in vivo selectivity of a new κ-opioid receptor antagonist PET tracer 11C-LY2795050 in the rhesus monkey.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- A positron emission tomography occupancy study of brexpiprazole at dopamine DNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Kinetic modeling of (11)C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Trial
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Numerical simulation method for the assessment of the effect of molar activity on the pharmacokinetics of radioligands in small animals.EJNMMI radiopharmacy and chemistry · 2024Article
- Clustering of KOR PET images separates people with AUD into distinct responses to naltrexone.Brain imaging and behavior · 2023Article
- Pleiotropic Effects of Kappa Opioid Receptor-Related Ligands in Non-human Primates.Handbook of experimental pharmacology · 2022Article
- Imaging Kappa Opioid Receptors in the Living Brain with Positron Emission Tomography.Handbook of experimental pharmacology · 2022Review
- A local-neighborhood Lassen plot filter for creating occupancy and non-displaceable binding images.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Synthesis and Pharmacological Evaluation of Fluorinated Quinoxaline-Based κ-Opioid Receptor (KOR) Agonists Designed for PET Studies.ChemMedChem · 2020Article
- Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development.European journal of nuclear medicine and molecular imaging · 2020Review
- A Survey of Molecular Imaging of Opioid Receptors.Molecules (Basel, Switzerland) · 2019Review
- Impact of Pharmacological Manipulation of theThe Journal of pharmacology and experimental therapeutics · 2019Article
- Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.Frontiers in psychiatry · 2019Review
- Radiosynthesis of [ACS medicinal chemistry letters · 2018Article
- PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Opioid system and human emotions.British journal of pharmacology · 2018Review
- (11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals.Chemical Society reviews · 2016Review
- Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050.The Journal of pharmacology and experimental therapeutics · 2016Article
- PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.American journal of nuclear medicine and molecular imaging · 2016Article
- PET Neurochemical Imaging Modes.Seminars in nuclear medicine · 2016Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelled(11)C-LY2795050 is a novel κ-selective antagonist PET tracer. The in vitro binding affinities (Ki) of LY2795050 at the κ-opioid (KOR) and μ-opioid (MOR) receptors are 0.72 and 25.8 nM, respectively. Thus, the in vitro KOR/MOR binding selectivity is about 36:1. Our goal in this study was to determine the in vivo selectivity of this new KOR antagonist tracer in the monkey.
methodsTo estimate the ED50 value (dose of a compound [or drug] that gives 50% occupancy of the target receptor) of LY2795050 at the MOR and KOR sites, 2 series of blocking experiments were performed in 3 rhesus monkeys using (11)C-LY2795050 and (11)C-carfentanil with coinjections of various doses of unlabeled LY2795050. Kinetic modeling was applied to calculate regional binding potential (BP(ND)), and 1- and 2-site binding curves were fitted to these data to measure (11)C-LY2795050 binding selectivity.
resultsThe LY2795050 ED50 at MOR was 119 μg/kg based on a 1-site model for (11)C-carfentanil. The 1-site binding model was also deemed sufficient to describe the specific binding of (11)C-LY2795050 at KOR. The ED50 at KOR estimated from the 1-site model was 15.6 μg/kg. Thus, the ED50 ratio for MOR:KOR was 7.6.
conclusionThe in vivo selectivity of (11)C-LY2795050 for KOR over MOR is 7.6. (11)C-LY2795050 has 4.7-fold-lower selectivity at KOR over MOR in vivo as compared with in vitro. Nevertheless, on the basis of our finding in vivo, 88% of the PET-observed specific binding of (11)C-LY2795050 under baseline conditions will be due to binding of the tracer at the KOR site in a region with similar prevalence of KOR and MOR. (11)C-LY2795050 is sufficiently selective for KOR over MOR in vivo to be considered an appropriate probe for studying the KOR with PET.
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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.