title: Ex vivo and in vivo evaluation of [18F]PR04.MZ in rodents: a selective dopamine transporter imaging agent.
abstract: N-4-Fluorobut-2-yn-1-yl-2beta-carbomethoxy-3beta-phenyltropane (PR04.MZ) has been developed as dopamine transporter (DAT) ligand for molecular imaging. It contains a terminally fluorinated, conformationally constrained nitrogen substituent that is well suited for the introduction of fluorine-18. The present report describes the pharmacological characterisation of [18F]PR04.MZ. The ligand shows an IC50 value of 2 nM against human DAT, whereas the IC50 value against human serotonin transporter and human noradrenalin transporter are lower (110 nM and 22 nM, respectively). Furthermore, its ex vivo organ distribution, its binding profile in the rat brain and reversibility of binding were examined. A muPET study illuminates a fast kinetic profile and specific binding to rat DAT.
authors: Universität Mainz-Institut für Kernchemie, Fritz Strassmann Weg 2, 55128 Mainz, Germany. riss@uni-mainz.de
authors: Patrick J
authors: PJ
authors: Riss
authors: Fabian
authors: F
authors: Debus
authors: René
authors: R
authors: Hummerich
authors: Ulrich
authors: U
authors: Schmidt
authors: Patrick
authors: P
authors: Schloss
authors: Hartmut
authors: H
authors: Lueddens
authors: Frank
authors: F
authors: Roesch
mesh_terms: D000818:Animals; D002460:Cell Line; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014326:Tropanes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C545366:PR04.MZ compound; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes