title: Characterisation of [¹¹C]PR04.MZ in Papio anubis baboon: a selective high-affinity radioligand for quantitative imaging of the dopamine transporter.
abstract: N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4'-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [(11)C]PR04.MZ ([(11)C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [(11)C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f(P)), plasma input functions and metabolic degradation of the radiotracer [(11)C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V(T)) and non-displaceable binding potentials (BP(ND)) for various brain regions and the blood were obtained from kinetic modelling. [(11)C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Riss
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: Colleen
authors.initials: C
authors.lastname: Shea
authors.forename: Youwen
authors.initials: Y
authors.lastname: Xu
authors.forename: Pauline
authors.initials: P
authors.lastname: Carter
authors.forename: Donald
authors.initials: D
authors.lastname: Warner
authors.forename: Valentina
authors.initials: V
authors.lastname: Ferrari
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Franklin I
authors.initials: FI
authors.lastname: Aigbirhio
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Frank
authors.initials: F
authors.lastname: Roesch
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D002247:Carbon Isotopes / Q000737:chemistry; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D015195:Drug Design; D005260:Female; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D048530:Papio anubis; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011522:Protons; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D014326:Tropanes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002247:Carbon Isotopes; D050483:Dopamine Plasma Membrane Transport Proteins; C545366:PR04.MZ compound; D011522:Protons; D019275:Radiopharmaceuticals; D014326:Tropanes