Molecular Imaging and Biology

, Volume 15, Issue 4, pp 376–383

Preclinical Safety Assessment of the 5-HT2A Receptor Agonist PET Radioligand [11C]Cimbi-36

  • Anders Ettrup
  • Søren Holm
  • Martin Hansen
  • Muhammad Wasim
  • Martin Andreas Santini
  • Mikael Palner
  • Jacob Madsen
  • Claus Svarer
  • Jesper Langgaard Kristensen
  • Gitte Moos Knudsen
Brief Article

DOI: 10.1007/s11307-012-0609-4

Cite this article as:
Ettrup, A., Holm, S., Hansen, M. et al. Mol Imaging Biol (2013) 15: 376. doi:10.1007/s11307-012-0609-4

Abstract

Purpose

[11C]Cimbi-36 was recently developed as an agonist radioligand for brain imaging of serotonin 2A receptors (5-HT2A) with positron emission tomography (PET). This may be used to quantify the high-affinity state of 5-HT2A receptors and may have the potential to quantify changes in cerebral 5-HT levels in vivo. We here investigated safety aspects related to clinical use of [11C]Cimbi-36, including radiation dosimetry and in vivo pharmacology.

Procedures

[11C]Cimbi-36 was injected in rats or pigs, and radiation dosimetry was examined by ex vivo dissection or with PET scanning, respectively. Based on animal data, the Organ Level INternal Dose Assessment software was used to estimate extrapolated human dosimetry for [11C]Cimbi-36. The 5-HT2A receptor agonist actions of [11C]Cimbi-36 in vivo pharmacological effects in mice elicited by increasing doses of Cimbi-36 were assessed with the head-twitch response (HTR).

Results

The effective dose as extrapolated from both rat and pig data was low, 7.67 and 4.88 μSv/MBq, respectively. In addition, the estimated absorbed radiation dose to human target organs did not exceed safety levels. Administration of 0.5 mg/kg Cimbi-36 leads to significant HTR compared to saline, whereas 0.05 mg/kg Cimbi-36 (doses much larger than those given in conjunction with a PET scan) did not elicit a significant HTR.

Conclusions

Administration of tracer doses of [11C]Cimbi-36 does not seem to be associated with unusual radiation burden or adverse clinical effects.

Key words

PETSerotonin receptorsHallucinogenicRadiation dosimetryHead-twitch responsePorcine

Copyright information

© World Molecular Imaging Society 2013

Authors and Affiliations

  • Anders Ettrup
    • 1
  • Søren Holm
    • 2
  • Martin Hansen
    • 3
  • Muhammad Wasim
    • 1
  • Martin Andreas Santini
    • 1
  • Mikael Palner
    • 1
  • Jacob Madsen
    • 2
  • Claus Svarer
    • 1
  • Jesper Langgaard Kristensen
    • 3
  • Gitte Moos Knudsen
    • 1
  1. 1.Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi)Copenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.PET and Cyclotron UnitCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  3. 3.Department of Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark