Synthesis and biological evaluation of 2beta,3alpha-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents.
A series of 2beta,3alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [(11)C]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [(11)C]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET.
Zeng
Fanxing
F
Department of Radiology, Division of Radiological Sciences, Emory University, 1364 Clifton Road, Atlanta, GA 30322, USA.
Stehouwer
Jeffrey S
JS
Jarkas
Nachwa
N
Voll
Ronald J
RJ
Williams
Larry
L
Camp
Vernon M
VM
Votaw
John R
JR
Owens
Michael J
MJ
Kilts
Clinton D
CD
Nemeroff
Charles B
CB
Goodman
Mark M
MM
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D002250:Carbon Radioisotopes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D003952:Diagnostic Imaging; D006801:Humans; D008253:Macaca mulatta; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000032:analysis*; D009662:Nortropanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography
D002250:Carbon Radioisotopes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009662:Nortropanes