Preclinical Safety Assessment of the 5-HT(2A) Receptor Agonist PET Radioligand [ (11)C]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

doi:10.1007/s11307-012-0609-4

Preclinical Safety Assessment of the 5-HT(2A) Receptor Agonist PET Radioligand [ (11)C]Cimbi-36

Authors:

Ettrup, Anders ;
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Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
Holm, Søren ;
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Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Hansen, Martin ;
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0000-0002-4663-8742
Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet
Wasim, Muhammad ;
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Rigshospitalet
Santini, Martin Andreas ;
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Rigshospitalet
Palner, Mikael ;
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Madsen, Jacob ;
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Rigshospitalet
Svarer, Claus ;
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Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
Kristensen, Jesper Langgaard ;
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0000-0002-5613-1267
Medicinal Chemistry Research, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet
Knudsen, Gitte Moos
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Rigshospitalet

DOI:

10.1007/s11307-012-0609-4

Abstract:

PURPOSE: [(11)C]Cimbi-36 was recently developed as an agonist radioligand for brain imaging of serotonin 2A receptors (5-HT(2A)) with positron emission tomography (PET). This may be used to quantify the high-affinity state of 5-HT(2A) 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 [(11)C]Cimbi-36, including radiation dosimetry and in vivo pharmacology. PROCEDURES: [(11)C]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 [(11)C]Cimbi-36. The 5-HT(2A) receptor agonist actions of [(11)C]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 [(11)C]Cimbi-36 does not seem to be associated with unusual radiation burden or adverse clinical effects.

Type:

Journal article

Language:

English

Published in:

Molecular Imaging and Biology, 2013, Vol 15, Issue 4, p. 376-83

Keywords:

Journal Article; Research Support, Non-U.S. Gov't

Main Research Area:

Medical science

Publication Status:

Published

Review type:

Peer Review

Submission year:

2013

Scientific Level:

Scientific

ID:

247479294

Preclinical Safety Assessment of the 5-HT(2A) Receptor Agonist PET Radioligand [ (11)C]Cimbi-36

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