ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2014
(11)C-CUMI-101, a PET radioligand, behaves as a serotonin 1A receptor antagonist and also binds to α(1) adrenoceptors in brain.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- [European journal of nuclear medicine and molecular imaging · 2023Article
- Article
- Examining the underpinnings of loudness dependence of auditory evoked potentials with positron emission tomography.NeuroImage · 2020Article
- Synthesis, in vitro and in vivo evaluation ofEJNMMI radiopharmacy and chemistry · 2020Article
- Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging.Medicinal research reviews · 2019Review
- In vivo biased agonism at 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Effect of Citalopram on Emotion Processing in Humans: A Combined 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States.The international journal of neuropsychopharmacology · 2016Article
- The 5-HT1A Receptor PET Radioligand 11C-CUMI-101 Has Significant Binding to α1-Adrenoceptors in Human Cerebellum, Limiting Its Use as a Reference Region.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2016Article
- Autoradiographic Evaluation of [(18)F]FECUMI-101, a High Affinity 5-HT1AR Ligand in Human Brain.ACS medicinal chemistry letters · 2016Article
- Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging.Current medicinal chemistry · 2016Review
- Application of cross-species PET imaging to assess neurotransmitter release in brain.Psychopharmacology · 2015Review
- PET tracers for serotonin receptors and their applications.Central nervous system agents in medicinal chemistry · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledThe PET radioligand (11)C-CUMI-101 was previously suggested as a putative agonist radioligand for the serotonin 1A (5-hydroxytryptamine 1A [5-HT1A]) receptor in recombinant cells expressing human 5-HT1A receptor. However, a recent study showed that CUMI-101 behaved as a potent 5-HT1A receptor antagonist in rat brain. CUMI-101 also has moderate affinity (Ki = 6.75 nM) for α1 adrenoceptors measured in vitro. The current study examined the functional properties and selectivity of CUMI-101, both in vitro and in vivo.
methodsThe functional assay was performed using (35)S-GTPγS (GTP is guanosine triphosphate) in primate brains. The cross-reactivity of CUMI-101 with α1 adrenoceptors was performed using in vitro radioligand binding studies in rat, monkey, and human brains as well as in vivo PET imaging in mouse, rat, and monkey brains.
resultsCUMI-101 did not stimulate (35)S-GTPγS binding in primate brain, in contrast to 8-OH-DPAT, a potent 5-HT1A receptor agonist. Instead, CUMI-101 behaved as a potent 5-HT1A receptor antagonist by dose-dependently inhibiting 8-OH-DPAT-stimulated (35)S-GTPγS binding. Both in vitro and in vivo studies showed that CUMI-101 had significant α1 adrenoceptor cross-reactivity. On average, across all 3 species examined, cross-reactivity was highest in the thalamus (>45%) and lowest in the neocortex and cerebellum (<10%). PET imaging further confirmed that only preblocking with WAY-100635 plus prazosin decreased (11)C-CUMI-101 brain uptake to that of self-block.
conclusionCUMI-101 behaves as a 5-HT1A receptor antagonist in primate brain, with significant, regional-dependent α1 adrenoceptor cross-reactivity, limiting its potential use as a PET radioligand in humans.
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