Reference : Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors
Scientific congresses and symposiums : Poster
Physical, chemical, mathematical & earth Sciences : Chemistry
Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors
Goblet, David mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Thonon, David mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Plenevaux, Alain mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Lemaire, Christian mailto [Université de Liège - ULiège > > Centre de recherches du cyclotron >]
Defraiteur, Caroline mailto [GE Healthcare MDX Chemistry Systems > > > >]
Wouters, Ludovic mailto [GE Healthcare MDX Chemistry Systems > > > >]
Franci, Xavier mailto [GE Healthcare MDX Chemistry Systems > > > >]
Luxen, André mailto [Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron >]
5TH European Molecular Imaging Meeting
from 26-05-2010 to 29-05-2010
European Society for Molecular Imaging
[en] positron emission tomography ; serotonin ; molecular imaging
[en] TOPIC: Molecular Neuroimaging: from Bench to Bedside
Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors

Introduction: Dysfunction of the cerebral serotoninergic system is implicated in numerous neurodegenerative disorders such as Alzheimer disease’s, dementia, depression, anxiety, schizophrenia, and Parkinson disease’s. The 5-HT1A serotonin receptors are involved in several physiological functions including sleep, mood, neurogenesis and learning [1]. Consequently, there have been huge efforts in finding ligands for this receptor. [11C]WAY-100635 is a high affinity radioligand used for quantifying serotonin 5-HT1A receptors with positron emission tomography. An 18F-labeled radioligand is advantageous because of higher specific activity and physical/nuclear properties (t1/2= 109 min, 97% of positron decay and positron energy of 635 keV maximum). [18F]MPPF, a selective 5-HT1A antagonist derived from WAY-100635, is currently one of the most successful PET ligand used for 5-HT1A receptor imaging [2]. However the affinity is lower then WAY-100635 and the amount of [18F]MPPF reaching the brain is relatively low since MPPF is a substrate for p-glycoprotein [3].

Methods: In order to improve the brain uptake of the radiotracer, a desmethylated analog has been developed in our lab and preliminary in vitro studies show positive results [4]. Nevertheless, the radiosynthesis take place in two steps as a protecting group removal is needed. A one step procedure with a MPPF derivative could be of very great interest. We have synthesized many MPPF derivatives in our lab (modification on the phenylpiperazine moiety) and developed an automated radiosynthesis procedure for the production of these radiotracers. [18F]MPPF was chosen as the model compound. We used a GE Healthcare FASTlabTM module and made modifications to the [18F]FDG synthesis sequence and cassette. [18F]MPPF was synthesized by coupling of [18F]FBA with the corresponding amine. After coupling, the crude solution was diluted with water and passed through a tC18 cartridge for prepurification. After elution, the [18F]MPPF was purified by semi-preparative HPLC.

Results: Total synthesis time, including purification was approximately 100 min. [18F]FBA and [18F]MPPF were obtained at a corrected yield of 55% (n=20) and 25% (n=5) respectively. The radiochemical purity, checked by radio-TLC and UPLC, was >95%.

Conclusions: We have developed an automated method for [18F]MPPF and derivatives production using a commercial synthesizer (FASTlabTM from GE Healthcare) and a conventional HPLC system resulting in good yields and high (radio)chemical purity. By simply switching the vial containing the modified amine, an 18F-labeled MPPF derivative could be obtained. Radiosynthesis is still under optimization and the radiotracers synthesized need to be tested as suitable 5-HT1A radioligands.

Acknowledgement: This work was supported by the Fondation Rahier.

[1] Filip M., Bader M. et Al, Pharmacol Rep. 2009 Sep-Oct; 61(5):761-77
[2] Aznavour N, Zimmer L. Et Al, Neuropharmacology. 2007 Mar; 52(3):695-707
[3] Laćan G., Plenevaux A. et Al, Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66
[4] Defraiteur C., Plenevaux A. et Al., Br J Pharmacol. 2007 Nov; 152(6):952-8
Centre de Recherches du Cyclotron - CRC
Fondation rahier - GE Healthcare MDX Chemistry Systems
Automated radiosynthesis of CNS ligands labeled with fluorine-18
Researchers ; Professionals ; Students

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