Characterisation of [ 11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

Patrick J. Riss, Jacob M. Hooker, Colleen Shea, Youwen Xu, Pauline Carter, Donald Warner, Valentina Ferrari, Sung Won Kim, Franklin I. Aigbirhio, Joanna S. Fowler, Frank Roesch

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 [ 11C]PR04.MZ ([ 11C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [ 11C]-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 [ 11C]-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. [ 11C]-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.

Original languageEnglish
Pages (from-to)679-682
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number1
DOIs
StatePublished - 1 Jan 2012
Externally publishedYes

Keywords

  • Carbon-11
  • Dopamine transporter
  • Non-human primates
  • PET imaging

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