[¹¹C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient ¹¹C-O-methylation and initial small animal PET studies

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [¹¹C]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 [¹¹C]MeI mediated synthesis of [¹¹C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb₂CO₃ in DMF in up to 95 ± 5% labelling yield. A preliminary μPET-experiment demonstrates the reversible, highly specific binding of [¹¹C]PR04.MZ in the brain of a male Sprague-Dawley rat.