Preparation and preliminary biological evaluation of [18F]NCQ-115: a new selective reversible dopamine D2 receptor ligand.
18F-labeled dopamine D2 antagonist, NCQ-115 ((+)-(R)-5-bromo-N-((1-(fluorobenzyl)-2-pyrrolidinyl)-methyl-2,3- dimethoxybenzamide), was successfully prepared using a remotely controlled system. [18F]Fluoride was reacted with the trifluoromethanesulfonate salt of 4-(trimethylamino)benzaldehyde. The product was first reduced with LAH, and then reacted with thionyl bromide to yield 18F-labeled 4-fluorobenzylbromide. [18F]4-Fluorobenzylbromide was then reacted with the pyrrolidie precursor (NCQ-282) to yield the product [18F]NCQ-115 contaminated with unreacted starting material. The product was purified by reverse phase chromatography yielding [18F]NCQ-115 with a specific activity of more than 1400 Ci/mmol. Autoradiographic and biodistribution data following injection of [18F]NCQ-115 in rats revealed the regional uptake of striatum/cerebellum to be 3.2 at 30 min post-injection.
Department of Psychiatry, University of California, Irvine 92717.
A
A
Najafi
A
A
Peterson
M
M
Buchsbaum
S
S
O'Dell
F
F
Weihmuller
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012680:Sensitivity and Specificity
D001549:Benzamides; D005462:Fluorine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C073230:5-bromo-2,3-dimethoxy-N-((1-(4-fluorobenzyl)-2-pyrrolidinyl)methyl)benzamide