title: [18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects.
abstract: We have characterized the usage of [18F]CFT (also known as [18F]WIN 35,428) as a radioligand for in vivo studies of human dopamine transporter by PET. CFT was labeled with 18F to a high specific activity, and dynamic PET scans were conducted in healthy volunteers at various time points up to 5 h from [18F]CFT injection. The regional distribution of [18F]CFT uptake correlated well with the known distribution of dopaminergic nerve terminals in the human brain and also with that of other dopamine transporter radioligands. Striatal binding peaked at 225 min after injection and declined thereafter, demonstrating the reversible nature of the binding to the dopamine transporter. Therefore, due to the relatively long half-life of 18F (109.8 min), PET scans with [18F]CFT could easily be conducted during the binding equilibrium, allowing estimation of Bmax/Kd values (i.e., binding potential). Binding potentials for putamen and caudate measured at equilibrium were 4.79+/-0.11 and 4.50+/-0.23, respectively. We were able to also visualize midbrain dopaminergic neurons (substantia nigra) with [18F]CFT in some subjects. In conclusion, the labeling of CFT with 18F allows PET scans to be conducted at binding equilibrium, and therefore a high signal-to-noise ratio and reliable quantification of binding potential can be achieved. With a high resolution 3D PET scanner, the quantification of extrastriatal dopamine transporters should become possible.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland. akilaa@utu.fi
authors.forename: A
authors.initials: A
authors.lastname: Laakso
authors.forename: J
authors.initials: J
authors.lastname: Bergman
authors.forename: M
authors.initials: M
authors.lastname: Haaparanta
authors.forename: H
authors.initials: H
authors.lastname: Vilkman
authors.forename: O
authors.initials: O
authors.lastname: Solin
authors.forename: J
authors.initials: J
authors.lastname: Hietala
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000502:physiology*; D003042:Cocaine / Q000031:analogs & derivatives*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D005260:Female; D005462:Fluorine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000737:chemistry / Q000000981:diagnostic imaging; D009419:Nerve Tissue Proteins / Q000502:physiology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000000981:diagnostic imaging; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: 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