title: [(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies.
abstract: PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [(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 [(11)C]MeI mediated synthesis of [(11)C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb(2)CO(3) in DMF in up to 95+/-5% labelling yield. A preliminary muPET-experiment demonstrates the reversible, highly specific binding of [(11)C]PR04.MZ in the brain of a male Sprague-Dawley rat.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. riss@uni-mainz.de
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Riss
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: David
authors.initials: D
authors.lastname: Alexoff
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
mesh_terms: D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002247:Carbon Isotopes / Q000737:chemistry; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008745:Methylation; D008956:Models, Chemical; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D011869:Radioligand Assay / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014326:Tropanes
chemical_list: D053961:Azabicyclo Compounds; D002247:Carbon Isotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; C545366:PR04.MZ compound; D014326:Tropanes