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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-08

AUTHORS

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

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. More... »

PAGES

376-383

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-012-0609-4

DOI

http://dx.doi.org/10.1007/s11307-012-0609-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003725749

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23306971


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