Synthesis and evaluation of (18)F-labeled bile acid compound: a potential PET imaging agent for FXR-related diseases.
The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily. The FXR has critical functions in maintaining bile acid synthesis and homeostasis, liver regeneration and tumorigenesis, intestinal diseases, intestinal tumorigenesis, cholesterol gallstone disease, cholestasis, and atherosclerosis. FXR expression is strongly downregulated in liver fibrosis, hepatocellular adenoma and hepatocellular carcinoma compared to expression levels in adjacent normal tissues. Chenodeoxycholic acid (CDCA) is the most potent physiological ligand for FXR. CDCA was radiolabeled with (18)F based on the efficiency click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides for noninvasively evaluating the relationship between FXR and FXR-related disease. The PET tracer [(18)F]8 was produced by 'click' labeling and showed a high non-decay corrected radiochemical yield (end of synthesis (EOS) yield=42±3% (n=5) from aqueous [(18)F]fluoride), high radiochemical purity ( >99%), and high specific activity (>320GBq/μmol). [(18)F]8 had a high metabolic stability in vitro and in vivo. PET imaging studies in nude mice indicated a rapid uptake of the tracer into liver tissue with uniform distribution of radioactivity in the liver. Significant accumulation of radioactivity was found in the liver, gallbladder, and intestine, while no obvious uptake was observed in other organs, such as the bladder, heart, and brain. Thus, this PET tracer represents a novel tool for early detection of abnormalities in the liver and staging of neoplasms.
Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences, Shanghai 201800, P. R. China; Graduate University of the Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, P. R. China.
Lina
L
Jia
Shanghai Institute of Applied Physics (SINAP), Chinese Academy of Sciences, Shanghai 201800, P. R. China; Graduate University of the Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, P. R. China.
Dawei
D
Jiang
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
Pengcheng
P
Hu
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
Xiao
X
Li
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
Hongcheng
H
Shi
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China. Electronic address: cheng.dengfeng@zs-hospital.sh.cn.
Dengfeng
D
Cheng
Graduate University of the Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, P. R. China. Electronic address: zhanglan@sinap.ac.cn.
Lan
L
Zhang
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes; D057927:Hydrophobic and Hydrophilic Interactions; D008107:Liver Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D005462:Fluorine Radioisotopes; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
(18)F; Bile acid; CDCA; Click chemistry; FXR; PET imaging