Olivier Tirel

Publications (2)8.07 Total impact

• Article: Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-[18F]-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors.

  Romain Labas, Gwénaëlle Gilbert, Olivier Nicole, Martine Dhilly, Ahmed Abbas, Olivier Tirel, Alain Buisson, Joël Henry, Louisa Barré, Danièle Debruyne, Franck Sobrio
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  ABSTRACT: In this study, novel specific PET radioligands containing the 4-(4-fluorobenzyl)piperidine moiety and selectively antagonistic for the NR2B subunit containing NMDA receptors were developed. Two antagonists, RGH-896 (1a) and 4-(4-fluorobenzyl)piperidinyl-1-methyl-2-benzimidazol-5-ol (2a), belonging to two different structural families, were radiolabeled by an aromatic nucleophilic radiofluorination followed by a reduction of the para-position carbonyl function. Radiotracers [18F]1a, [18F]2a or the pattern 4-(4-[18F]-fluorobenzyl)piperidine ([18F]6) demonstrated an identical in vivo behavior with high accumulation of radioactivity in bone and cartilage which would suggest a radiodefluorination of the radiotracers. The identification of metabolites from 6 by LC-MS-MS confirmed the significant degree of defluorination as a result of the in vivo hydroxylation in the benzyl ring. In conclusion, [18F]1a or [18F]2a are not suitable for imaging the NR2B NMDA receptors due to their poor brain penetration. We also argue for a cautious use of the radiolabeled pattern, 4-(4-[18F]-fluorobenzyl)piperidine, to develop PET radiotracers.
  European journal of medicinal chemistry 03/2011; 46(6):2295-309. · 3.27 Impact Factor
• Article: Chemical delivery system of metaiodobenzylguanidine (MIBG) to the central nervous system.

  Fabienne Gourand, Guillaume Mercey, Méziane Ibazizène, Olivier Tirel, Joël Henry, Vincent Levacher, Cécile Perrio, Louisa Barré
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  ABSTRACT: The aim of the present investigation was to apply a chemical delivery system (CDS) to MIBG (4) with the purpose of delivering this drug to the CNS. Compound 4 has been linked to a 1,4-dihydroquinoline moiety in order to achieve its CNS penetration, and here we report the synthesis to link 4 to the chemical delivery system and the radiosynthesis with carbon-11 of the "CDS-4 entity". After iv injection into rats of the [(11)C]CDS-4, the follow-up study of the radioactivity distribution in blood samples and brain homogenates and the analysis by HPLC and LC-MS/MS have confirmed the release of 4 into the CNS.
  Journal of Medicinal Chemistry 02/2010; 53(3):1281-7. · 4.80 Impact Factor