Fluorine-18-labelled NCQ 115, a selective dopamine D-2 receptor ligand. Preparation and positron emission tomography.
NCQ 115 ((+)-(R)-5-bromo-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)-2, 3-dimethoxybenzamide) is a selective dopamine D-2 receptor antagonist. NCQ 115 has a fluorine in a synthetically suitable position in the parent compound and was therefore suggested as a potential 18F-labelled radioligand for positron emission tomography (PET). [18F]4-Fluorobenzyl iodide was prepared in a 3-step synthesis from [18F]fluoride. N-4-Fluorobenzylation of the corresponding secondary pyrrolidine precursor was performed in DMF followed by purification with semi-preparative HPLC. The total radiochemical yield (EOB and decay-corrected) was 15-20% with a total synthesis time of 90 min and a radiochemical purity > 99%. The specific radioactivity at the end of synthesis (EOS) was about 1500 Ci/mmol (55.5 GBq/mumol). [18F]NCQ 115 was injected into a Cynomolgus monkey for PET examination of brain in vivo. There was a conspicuous uptake of radioactivity in the monkey striatum. A specific [18F]NCQ 115 binding reached a peak after about 60 min which indicates equilibrium.
Halldin
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Karolinska Institute, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Högberg
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Farde
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D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008252:Macaca fascicularis; D008297:Male; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D001549:Benzamides; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes; D008024:Ligands; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C073230:5-bromo-2,3-dimethoxy-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)benzamide