Confirmation of fenfluramine effect on 5-HT(1B) receptor binding of [(11)C]AZ10419369 using an equilibrium approach.


Assessment of serotonin release in the living brain with positron emission tomography (PET) may have been hampered by the lack of suitable radioligands. We previously reported that fenfluramine caused a dose-dependent reduction in specific binding in monkeys using a classical displacement paradigm with bolus administration of [(11)C]AZ10419369. The aim of this study was to confirm our previous findings using an equilibrium approach in monkey. A total of 24 PET measurements were conducted using a bolus infusion protocol of [(11)C]AZ10419369 in three cynomolgus monkeys. Initial PET measurements were performed to assess suitable K(bol) values. The fenfluramine effect on [(11)C]AZ10419369 binding was evaluated in a displacement and pretreatment paradigm. The effect of fenfluramine on [(11)C]AZ10419369 binding potential (BP(ND)) was dose-dependent in the displacement paradigm and confirmed in the pretreatment paradigm. After pretreatment administration of fenfluramine (5.0 mg/kg), the mean BP(ND) of the occipital cortex decreased by 39%, from 1.38±0.04 to 0.84±0.09. This study confirms that the new 5-HT(1B) receptor radioligand [(11)C]AZ10419369 is sensitive to fenfluramine-induced changes in endogenous serotonin levels in vivo. The more advanced methodology is suitable for exploring the sensitivity limit to serotonin release as measured using [(11)C]AZ10419369 and PET.

DOI: 10.1038/jcbfm.2011.172

Extracted Key Phrases

7 Figures and Tables

Citations per Year

414 Citations

Semantic Scholar estimates that this publication has 414 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Finnema2012ConfirmationOF, title={Confirmation of fenfluramine effect on 5-HT(1B) receptor binding of [(11)C]AZ10419369 using an equilibrium approach.}, author={Sjoerd J. Finnema and Andrea Varrone and Tzung-Jeng Hwang and Christer Halldin and Lars Farde}, journal={Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, year={2012}, volume={32 4}, pages={685-95} }