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

Abstract: [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 48GBq/μmol 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-α) and π 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. [Copyright &y& Elsevier]