Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats.
BACKGROUND
The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo.


METHODS
The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP.


RESULTS
The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand.


CONCLUSIONS
The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.
Koivula
Teija
T
Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, PO Box 55, FI-00014 Helsinki, Finland.
Marjamäki
Päivi
P
Haaparanta
Merja
M
Fagerholm
Veronica
V
Grönroos
Tove
T
Lipponen
Tiina
T
Perhola
Outi
O
Vepsäläinen
Jouko
J
Solin
Olof
O
D000818:Animals; D001667:Binding, Competitive; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002531:Cerebellum / Q000000981:diagnostic imaging; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008032:Limbic System / Q000000981:diagnostic imaging; D008297:Male; D009662:Nortropanes / Q000493:pharmacokinetics; D010879:Piperazines / Q000494:pharmacology; D011869:Radioligand Assay / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005462:Fluorine Radioisotopes; D009662:Nortropanes; D010879:Piperazines; D019275:Radiopharmaceuticals; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; C043425:vanoxerine; D003042:Cocaine