Synthesis and evaluation of [¹⁸F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase

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• 作者：Ho-Lien Huang^a ; ^&dagger ; ; Chun-Nan Yeh^b ; ^&dagger ; ; Kang-Wei Chang^c ; Jenn-Tzong Chen^c ; Kun-Ju Lin^d ; Li-Wu Chiang^a ; Kee-Ching Jeng^e ; Wei-Ting Wang^f ; Ken-Hong Lim^f ; ^g ; Caleb Gonshen Chen^f ; ^g ; Kun-I Lin^a ; ^h ; Ying-Cheng Huangⁱ ; Wuu-Jyh Lin^c ; Tzu-Chen Yen^d ; Chung-Shan Yu^a ; ^j ; ^{csyu@mx.nthu.edu.tw}
• 关键词：CCA ; cholangiocarcinoma ; TAA ; thioacetamide ; NERI ; Nuclear Energy Research Institute ; CGMH ; Chang-Gung Memorial Hospital
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 June, 2012
• 卷：22
• 期：12
• 页码：3998-4003
• 文件大小：778 K

摘要

[¹⁸F]Flurobutyl ethacrynic amide ([¹⁸F]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/渭mol and radiochemical purity of 98%. Chemical conjugation of [¹⁸F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-伪) and 蟺 provided about 41%yields of radiochemical conjugated product [¹⁸F]FBuEA-GSH, 85%and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [¹⁸F]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 [¹⁸F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [¹⁸F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.