Details

Autor(en) / Beteiligte

• Riss, Patrick J.
• Debus, Fabian
• Hummerich, René
• Schmidt, Ulrich
• Schloss, Patrick
• Lueddens, Hartmut
• Roesch, Frank

Titel

Ex vivo and in vivo Evaluation of [18F]PR04.MZ in Rodents: A Selective Dopamine Transporter Imaging Agent

Ist Teil von

• ChemMedChem, 2009-09, Vol.4 (9), p.1480-1487

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2009

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• N‐4‐Fluorobut‐2‐yn‐1‐yl‐2β‐carbomethoxy‐3β‐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 μPET study illuminates a fast kinetic profile and specific binding to rat DAT. The PET imaging agent N‐4‐[18F]fluorobut‐2‐yn‐1‐yl‐2β‐carbomethoxy‐3β‐phenyltropane ([18F]PR04.MZ) binds in a highly specific and reversible manner to rodent dopamine transporters. This was established using in vitro, ex vivo and in vivo evaluation in rodents, in which the radioligand showed fast kinetics, good selectivity and reversible binding characteristics in the DAT‐rich brain regions of mice and rats.