Synthesis, radiosynthesis, and biological evaluation of carbon-11 and fluorine-18 (N-fluoroalkyl) labeled 2beta-carbomethoxy-3beta-(4'-(3-furyl)phenyl)tropanes and -nortropanes: candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography.
2beta-Carbomethoxy-3beta-(4'-(3-furyl)phenyl)nortropane (1) was synthesized along with the N-methyl (2), N-fluoroethyl (3), N-fluoropropyl (4), and N-fluorobutyl (5) derivatives. The binding affinity for each compound to the human serotonin, dopamine, and norepinephrine transporters was determined using transfected HEK-293 cells. Radiolabeling and microPET brain imaging studies were performed with [(11)C]1, [(11)C]2, and [(18)F]3 to determine their utility as in vivo imaging agents.
Stehouwer
Jeffrey S
JS
Department of Radiology, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322, USA.
Plisson
Christophe
C
Jarkas
Nachwa
N
Zeng
Fanxing
F
Voll
Ronald J
RJ
Williams
Larry
L
Martarello
Laurent
L
Votaw
John R
JR
Tamagnan
Gilles
G
Goodman
Mark M
MM
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D002460:Cell Line; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005462:Fluorine Radioisotopes; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008024:Ligands; D008252:Macaca fascicularis; D008253:Macaca mulatta; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D009662:Nortropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
C506296:2-carbomethoxy-3-(4'-(3-furyl)phenyl)nortropane; D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D005663:Furans; D008024:Ligands; C506298:N-(2-fluoroethyl)-2-carbomethoxy-3-(4'-(3-furyl)phenyl)nortropane; C506297:N-methyl-2-carbomethoxy-3-(4'-(3-furyl)phenyl)nortropane; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009662:Nortropanes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes