Synthesis and evaluation of ¹⁸ F-labeled bile acid compound: A potential PET imaging agent for FXR-related diseases

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• 作者：Lina Jia^a ; ^b ; Dawei Jiang^a ; ^b ; Pengcheng Hu^c ; Xiao Li^c ; Hongcheng Shi^c ; Dengfeng Cheng^c ; ^{cheng.dengfeng@zs-hospital.sh.cn" class="auth_mail} ; Lan Zhang^b ; ^{zhanglan@sinap.ac.cn" class="auth_mail}
• 关键词：Bile acid ; FXR ; PET imaging ; 18  ; F ; CDCA ; Click chemistry
• 刊名：Nuclear Medicine and Biology
• 出版年：July 2014
• 年：2014
• 卷：41
• 期：6
• 页码：495-500
• 全文大小：875 K

文摘

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 (> 320 GBq/渭mol). [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.