Preclinical safety assessment of the 5-HT2A receptor agonist PET radioligand [ 11C]Cimbi-36

Mol Imaging Biol. 2013 Aug;15(4):376-83. doi: 10.1007/s11307-012-0609-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / adverse effects*
  • Benzylamines / chemical synthesis
  • Benzylamines / chemistry
  • Benzylamines / pharmacokinetics
  • Dose-Response Relationship, Radiation
  • Humans
  • Ligands
  • Mice
  • Phenethylamines / adverse effects*
  • Phenethylamines / chemical synthesis
  • Phenethylamines / chemistry
  • Phenethylamines / pharmacokinetics
  • Positron-Emission Tomography*
  • Radiometry
  • Rats
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin 5-HT2 Receptor Agonists / adverse effects*
  • Serotonin 5-HT2 Receptor Agonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Agonists / chemistry
  • Serotonin 5-HT2 Receptor Agonists / pharmacokinetics
  • Sus scrofa
  • Tissue Distribution / drug effects
  • Whole Body Imaging


  • Benzylamines
  • Cimbi-36
  • Ligands
  • Phenethylamines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Agonists