Aminopyridines/pharmacokinetics; Animals; Autoradiography/methods; Biological Transport; Chromatography, High Pressure Liquid; Fluorine Radioisotopes/pharmacokinetics; Kinetics; Male; Microdialysis; Piperazines/pharmacokinetics; Radiation-Sensitizing Agents/pharmacokinetics; Raphe Nuclei/radionuclide imaging; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Serotonin/metabolism; Tissue Distribution
Abstract :
[en] The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal beta-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [(18)F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using beta-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the DRN of anaesthetised rodents.
Research Center/Unit :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège CERMEP Lyon
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Zimmer, L.
Pain, F.
Mauger, G.
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Le Bars, Didier; Centre d'Exploration et de Recherche Médicales par Émission de Positons - CERMEP (Lyon)
Mastrippolito, R.
Pujol, J. F.
Renaud, B.
Laniece, Philippe; Université Paris XI > Institut de Physique Nucléaire
Language :
English
Title :
The potential of the beta-Microprobe, an intracerebral radiosensitive probe, to monitor the [(18)F]MPPF binding in the rat dorsal raphe nucleus.
Publication date :
2002
Journal title :
European Journal of Nuclear Medicine and Molecular Imaging
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