Details

Autor(en) / Beteiligte

• Piel, Markus
• Schirrmacher, Ralf
• Höhnemann, Sabine
• Hamkens, Wilhelm
• Kohl, Beate
• Jansen, Michaela
• Schmitt, Ullrich
• Lüddens, Hartmut
• Dannhardt, Gerd
• Rösch, Frank

Titel

Synthesis and evaluation of 5,7-dichloro-4-(3-{4-[4-(2-[18F]fluoroethyl)-piperazin-1-yl]-phenyl}-ureido)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid as a potential NMDA ligand to study glutamatergic neurotransmission in vivo

Ist Teil von

• Journal of labelled compounds & radiopharmaceuticals, 2003-06, Vol.46 (7), p.645-659

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2003

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• The neurotransmitter glutamate is thought to be crucially involved in a huge number of neurological and psychiatric disorders, such as Morbus Parkinson, Alzheimer's disease and schizophrenia. Aiming at an improved diagnostic tool for PET a new [18F]fluorine labelled NMDA receptor ligand was developed that may potentially allow the in vivo visualization of glutama‐tergic neurotransmission. The 19F‐analogue trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydro quinoline‐2‐carboxylic acid was synthesised to determine the binding affinity, lipophilicity and biodistribution of the ligand. This substance exhibits a Ki of 12 nM for the glycine binding site using [3H]MDL‐105,519 assays on pig cortical membranes. A logD of 1.3 was determined for this compound according to the OECD guidelines employing the HPLC method. Radiosynthesis of this ligand was achieved by labelling the precursor trans‐5,7‐dichloro‐4‐[3‐(4‐piperazin‐1‐yl‐phenyl)‐ureido]‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid methyl ester with 2‐[18F]fluoroethyltosylate and subsequent cleaving of the methyl ester moiety, resulting in an overall decay corrected yield of 35% of the final product trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[18F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid. The biodistribution kinetics of this compound were determined with Sprague Dawley rats ex vivo for brain, liver, kidney, and bone. The ligand showed a maximum brain uptake 30 min.p.i. of about 0.1% ID/g. Copyright © 2003 John Wiley & Sons, Ltd.