Preparation and biological evaluation of 18F-labeled benzamide analogs as potential dopamine D2 receptor ligands.
Three 18F-labeled benzamide derivatives were prepared and evaluated as potential ligands to study the dopamine D2 receptor phenomenon. The compounds are analogs of iodobenzamide, eticlopride and raclopride and are labeled with an N-2-[18F]fluoroethyl functionality on the pyrrolidine ring. The compounds were tested in vitro for binding affinity and found to exhibit somewhat lower affinity than the non-fluorinated analog. In vivo distribution studies revealed that all compounds were more highly bound to plasma proteins than was raclopride. In addition, compartmentation of radioactivity demonstrated nonspecific binding to be the predominate retention in the brain as reflected by the low caudate to cerebellum ratios for these compounds. These three 18F-labeled benzamide derivatives are inferior to raclopride and iodobenzamide for studies of the D2 receptor system using positron emission tomography.
Kiesewetter
D O
DO
Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
Kawai
R
R
Chelliah
M
M
Owens
E
E
McLellan
C
C
Blasberg
R G
RG
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006801:Humans; D066298:In Vitro Techniques; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D014055:Tomography, Emission-Computed
D001549:Benzamides; D001798:Blood Proteins; D005462:Fluorine Radioisotopes; D008024:Ligands; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2