[18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: biodistribution in rats.
We describe the 18F-radiolabelling synthesis (18F; T(1/2) = 109.8 min) of 2-beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (also known as CFT or WIN 35,428) and the biodistribution of this compound in rats. 18F-labelled CFT has high chemical and radiochemical purity and relatively high specific radioactivity [specific radioactivity up to 14.8 GBq/mumol (400 mCi/mumol) at end of synthesis]. Striatum to cerebellum radioactivity uptake ratios were calculated from digitised images of rat brain slices recorded with a phosphoimaging device, the maximum ratio of about 10 was obtained at 2 h postinjection. Pretreatment of the rats with a specific dopamine transport inhibitor, GBR 12909, showed that CFT binding is specific in striatum. The highest accumulation of 18F-radioactivity was found in the liver, urine, striatum, and kidney of the rat. Clearance from blood was rapid. The uptake in bone was low, indicating that [18F]CFT is not defluorinated. The relatively long half-life of 18F makes it possible to study the uptake of [18F]CFT in the brain, as equilibrium between specific and non-specific binding is reached. This will improve the signal to noise ratio as compared to positron emission tomography (PET) studies with [11C]CFT (11C; T(1/2) = 20.4 min). CFT labelled with 18F is clearly a promising radioligand for PET studies of the dopamine transporter system in humans.
Haaparanta
M
M
Medical Cyclotron/PET Center, University of Turku, Finland.
Bergman
J
J
Laakso
A
A
Hietala
J
J
Solin
O
O
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine