Development of a New Thiol Site-Specific Prosthetic Group and Its Conjugation with [Cys40]-exendin-4 for in Vivo Targeting of Insulinomas

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• 作者：Xuyi Yue ; Dale O. Kiesewetter ; Jinxia Guo ; Zhongchan Sun ; Xiaoxiang Zhang ; Lei Zhu ; Gang Niu ; Ying Ma ; Lixin Lang ; Xiaoyuan Chen
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：July 17, 2013
• 年：2013
• 卷：24
• 期：7
• 页码：1191-1200
• 全文大小：433K
• 年卷期：v.24,no.7(July 17, 2013)
• ISSN：1520-4812

文摘

A new tracer, N-5-[¹⁸F]fluoropentylmaleimide ([¹⁸F]FPenM), for site-specific labeling of free thiol group in proteins and peptides was developed. The tracer was synthesized in three steps (¹⁸F displacement of the aliphatic tosylate, di-Boc removal by TFA to expose free amine, and incorporation of the free amine into a maleimide). The radiosynthesis was completed in 110 min with 11鈥?7% radiochemical yield (uncorrected), and specific activity of 20鈥?9 GBq/渭mol. [¹⁸F]FPenM showed comparable labeling efficiency with N-[2-(4-[¹⁸F]fluorobenzamido)ethyl]maleimide ([¹⁸F]FBEM). Its application was demonstrated by conjugation with glucagon-like peptide type 1 (GLP-1) analogue [cys⁴⁰]-exendin-4. The cell uptake, binding affinity, imaging properties, biodistribution, and metabolic stability of the radiolabeled [¹⁸F]FPenM-[cys⁴⁰]-exendin-4 were studied using INS-1 tumor cells and INS-1 xenograft model. Positron emission tomography (PET) results showed that the new thiol-specific tracer, [¹⁸F]FPenM-[cys⁴⁰]-exendin-4, had high tumor uptake (20.32 卤 4.36%ID/g at 60 min postinjection) and rapid liver and kidney clearance, which was comparable to the imaging results with [¹⁸F]FBEM-[cys⁴⁰]-exendin-4 reported by our group.