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Potential of [ 18 F]β‐CFT‐FE (2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐8‐(2‐[ 18 F]fluoroethyl)nortropane) as a dopamine transporter ligand: A PET study in the conscious monkey brain
Author(s) -
Harada Norihiro,
Ohba Hiroyuki,
Fukumoto Dai,
Kakiuchi Takeharu,
Tsukada Hideo
Publication year - 2004
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20059
Subject(s) - dopamine transporter , chemistry , ligand (biochemistry) , metabolite , norepinephrine transporter , dopamine , dopamine plasma membrane transport proteins , stereochemistry , nuclear chemistry , transporter , serotonin , medicine , biochemistry , receptor , gene
Abstract A dopamine transporter (DAT) ligand 2β‐carbomethoxy‐3β‐(4‐fluoro‐phenyl)‐8‐(2‐[ 18 F]fluoroethyl)nortropane ([ 18 F]β‐CFT‐FE) was synthesized and evaluated in comparison with [ 11 C]β‐CFT in monkey brain using animal positron emission tomography (PET). [ 18 F]β‐CFT‐FE and [ 11 C]β‐CFT were injected intravenously to conscious monkeys for a 91‐min PET scan with arterial blood sampling for metabolite analysis. In the conscious state, [ 18 F]β‐CFT‐FE provided a peak about 20 min after the injection and declined thereafter in the striatum of monkey brain, while [ 11 C]β‐CFT continuously increased with time up to 91 min after injection. Metabolite analysis revealed that [ 18 F]β‐CFT‐FE was more rapidly metabolized in plasma than [ 11 C]β‐CFT. The striatal binding of both ligands was dose‐dependently displaced by preadministration of a specific DAT inhibitor, GBR12909, at doses of 0.5 and 5 mg/kg; however, the displacement degree of [ 11 C]β‐CFT‐FE was higher than that of [ 18 F]β‐CFT. The effects of the anesthetics, ketamine and isoflurane, on binding were more prominent in [ 11 C]β‐CFT than [ 18 F]β‐CFT‐FE. Specificity and affinity of β‐CFT‐FE to DAT were evaluated in an in vitro assay using cloned human DAT, serotonin transporter, and norepinephrine transporter in comparison with other conventional DAT ligands, showing that β‐CFT‐FE had lower affinity and higher specificity to DAT than β‐CFT and β‐CIT. These results suggested that [ 18 F]β‐CFT‐FE could be a potential imaging agent for DAT, providing excellent selectivity and tracer kinetics for quantitative PET imaging. Synapse 54:37–45, 2004. © 2004 Wiley‐Liss, Inc.