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Costes, Nicolas; Merlet, Isabelle; Zimmer, Luc; Lavenne, Franck; Cinotti, Luc; Delforge, Jacques; Luxen, André; Pujol, Jean-François; Bars, Didier Le

Modeling [18F]MPPF Positron Emission Tomography Kinetics for the Determination of 5-Hydroxytryptamine(1A) Receptor Concentration with Multiinjection

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  • Media type: E-Article
  • Title: Modeling [18F]MPPF Positron Emission Tomography Kinetics for the Determination of 5-Hydroxytryptamine(1A) Receptor Concentration with Multiinjection
  • Contributor: Costes, Nicolas; Merlet, Isabelle; Zimmer, Luc; Lavenne, Franck; Cinotti, Luc; Delforge, Jacques; Luxen, André; Pujol, Jean-François; Bars, Didier Le
  • Published: SAGE Publications, 2002
  • Published in: Journal of Cerebral Blood Flow & Metabolism, 22 (2002) 6, Seite 753-765
  • Language: English
  • DOI: 10.1097/00004647-200206000-00014
  • ISSN: 0271-678X; 1559-7016
  • Keywords: Cardiology and Cardiovascular Medicine ; Neurology (clinical) ; Neurology
  • Origination:
  • Footnote:
  • Description: <jats:p> The selectivity of [<jats:sup>18</jats:sup>F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT<jats:sub>1A</jats:sub>) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [<jats:sup>18</jats:sup>F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: F<jats:sub>v</jats:sub> (vascular fraction), K<jats:sub>1</jats:sub>, k<jats:sub>2</jats:sub> (plasma/free compartment exchange rate), k<jats:sub>off</jats:sub>, k<jats:sub>on</jats:sub>/V<jats:sub>r</jats:sub> (association and dissociation rate), B<jats:sub>max</jats:sub> (receptor concentration), and to deduce K<jats:sub>d</jats:sub> (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT<jats:sub>1A</jats:sub> specificity for MPPF was evidenced. A B<jats:sub>max</jats:sub> of 2.9 pmol/mL and a K<jats:sub>d</jats:sub> of 2.8 nmol/L were found in hippocampal regions, K<jats:sub>d</jats:sub> and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to B<jats:sub>max</jats:sub>. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT<jats:sub>1A</jats:sub> receptors. Standard values can be used for the simulation of simplified protocols. </jats:p>