title: Synthesis and evaluation of [18F]Fluorobutyl ethacrynic amide: a potential PET tracer for studying glutathione transferase.
abstract: [(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu 300, Taiwan.
authors.forename: Ho-Lien
authors.initials: HL
authors.lastname: Huang
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Jenn-Tzong
authors.initials: JT
authors.lastname: Chen
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Chiang
authors.forename: Kee-Ching
authors.initials: KC
authors.lastname: Jeng
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Wang
authors.forename: Ken-Hong
authors.initials: KH
authors.lastname: Lim
authors.forename: Caleb Gonshen
authors.initials: CG
authors.lastname: Chen
authors.forename: Kun-I
authors.initials: KI
authors.lastname: Lin
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Huang
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Chung-Shan
authors.initials: CS
authors.lastname: Yu
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000000981:diagnostic imaging*; D001653:Bile Ducts, Intrahepatic / Q000000981:diagnostic imaging* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000175:diagnosis / Q000000981:diagnostic imaging*; D005462:Fluorine Radioisotopes; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000577:Amides; D005462:Fluorine Radioisotopes; D007527:Isoenzymes; D019275:Radiopharmaceuticals; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D005978:Glutathione