6533b7d3fe1ef96bd1261439
RESEARCH PRODUCT
[(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies.
Patrick J. RissSung Won KimJacob M. HookerJoanna S. FowlerFrank RöschDavid Alexoffsubject
MaleBiodistributionFluorine RadioisotopesTime FactorsStereochemistryClinical BiochemistryPharmaceutical ScienceBiochemistryChemical synthesisMethylationRats Sprague-Dawleychemistry.chemical_compoundRadioligand AssayDrug DiscoveryRadioligandTrifluoroacetic acidMoietyAnimalsMolecular BiologyDopamine transporterCarbon IsotopesDopamine Plasma Membrane Transport ProteinsbiologyBicyclic moleculeOrganic ChemistryBrainLigand (biochemistry)Magnetic Resonance ImagingRatschemistryModels ChemicalDrug DesignPositron-Emission Tomographybiology.proteinMolecular MedicineAzabicyclo CompoundsTropanesdescription
PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experiment demonstrates the reversible, highly specific binding of [{sup 11}C]PR04.MZ in the brain of a male Sprague-Dawley rat.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-08-01 | Bioorganicmedicinal chemistry letters |