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Cited by 7Neurotransmitter Receptor Influence on BehaviorMedical Imaging Techniques and ApplicationsRadiopharmaceutical Chemistry and Applications

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates

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Prabhakaran, Jaya, DeLorenzo, Christine, Zanderigo, Francesca, Knudsen, Gitte M, Gilling, Nic, Pratap, Mali, Jorgensen, Matthew J, Daunais, James +4 more·2019·Journal of Pharmacy & Pharmaceutical Sciences
DOI 10.18433/jpps30329PMC PMC7453972
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Abstract

PURPOSE: 5-HT2AR exists in high and low affinity states. Agonist PET tracers measure binding to the active high affinity site and thus provide a functionally relevant measure of the receptor. Limited in vivo data have been reported so far for a comparison of agonist versus antagonist tracers for 5-HT2AR used as a proof of principle for measurement of high and low affinity states of this receptor. We compared the in vivo binding of [11C]CIMBI-5, a 5-HT2AR agonist, and of the antagonist [11C]M100907, in monkeys and baboons. METHODS: [11C]CIMBI-5 and [11C]M100907 baseline PET scans were performed in anesthetized male baboons (n=2) and male vervet monkeys (n=2) with an ECAT EXACT HR+ and GE 64-slice PET/CT Discovery VCT scanners. Blocking studies were performed in vervet monkeys by pretreatment with MDL100907 (0.5 mg/kg, i.v.) 60 minutes prior to the scan. Regional distribution volumes and binding potentials were calculated for each ROI using the likelihood estimation in graphical analysis and Logan plot, with either plasma input function or reference region as input, and simplified reference tissue model approaches. RESULTS: PET imaging of [11C]CIMBI-5 in baboons and monkeys showed the highest binding in 5-HT2AR-rich cortical regions, while the lowest binding was observed in cerebellum, consistent with the expected distribution of 5-HT2AR. Very low free fractions and rapid metabolism were observed for [11C]CIMBI-5 in baboon plasma. Binding potential values for [11C]CIMBI-5 were 25-33% lower than those for [11C]MDL100907 in the considered brain regions. CONCLUSION: The lower binding potential of [11C]CIMBI-5 in comparison to [11C]MDL100907 is likely due to the preferential binding of the former to the high affinity site in vivo in contrast to the antagonist, [11C]MDL100907, which binds to both high and low affinity sites.

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  • Comparative PET of [11C]-Cimbi-5 and antagonist [11C]-MDL100907 in non-human primates found the antagonist ligand had two or three-fold higher BPND than [11C]-Cimbi-5 in most brain regions.

    “Others conducted a comparative PET study of [11C]-Cimbi-5 (34) and the antagonist [11C]-MDL100907 (35) in living non-human primates, finding that the antagonist ligand had two or three-fold higher BPND than [11C]-Cimbi-5 (34) in most brain regions [88]”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [88]

    The Results section (PET studies in baboon) reports that [11C]MDL100907 had higher BPND than [11C]CIMBI-5. It identifies three regions with differences of 56.1–61.7%, but the Abstract Results report [11C]CIMBI-5 binding potential as 25–33% lower overall. The source therefore supports the comparison and its direction, not a two- or three-fold difference in most brain regions. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Pretreatment with MDL100907 did not completely displace [11C]-Cimbi-5 binding in all brain regions, indicating somewhat incomplete selectivity.

    “pretreatment with MDL100907 did not completely displace [11C]-Cimbi-5 (34) binding in all brain regions, indicating somewhat incomplete selectivity.”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [88]

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Cited by

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Authors
Prabhakaran, J., DeLorenzo, C., Zanderigo, F., Knudsen, G. M., Gilling, N., Pratap, M., Jorgensen, M. J., Daunais, J., Kaplan, J. R., Parsey, R. V., Mann, J. J., & Kumar, D.
Affiliations
  • Columbia University Irving Medical Center (US)
  • Stony Brook University (US)
  • University of Copenhagen (DK)
  • Copenhagen University Hospital (DK)
  • New York State Psychiatric Institute (US)
  • Wake Forest University Health Sciences (US)
ORCID
Venue
Journal of Pharmacy & Pharmaceutical Sciences
Publisher
Frontiers Media SA
Published
2019-07-26
Volume
22
Issue
1
Pages
352-364
ISSN
1482-1826 (ISSN-L)
DOI
10.18433/jpps30329
PMC
PMC7453972
OpenAlex
W2966044403
Cited by
7
References
6
Citations by year
2026: 1 · 2023: 1 · 2022: 4 · 2021: 1
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Pharmacy & Pharmaceutical Sciences (publishedVersion, cc-by)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (UL1TR001420, P40OD010965)
  • National Institute of Mental Health (R21MH091470)
  • National Institute on Drug Abuse (R21DA041670)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Keywords
5-HT2A receptor, serotonin receptor agonists, binding potential, non-human primates, baboons, vervet monkey, radiotracer biodistribution
MeSH terms
Animals, Haplorhini, Brain, Carbon Radioisotopes, Dimethoxyphenylethylamine, Papio, Tissue Distribution, Radiopharmaceuticals, Receptor, Serotonin, 5-HT2B, Positron-Emission Tomography, Serotonin 5-HT2 Receptor Agonists

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