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 [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 (fP), 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 (VT) and non-displaceable binding potentials (BPND) 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.