Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe 18F-FBEM–Cys39-exendin-4
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- 作者：Yuping Xu (1)
Donghui Pan (1)
Qing Xu (2)
Chen Zhu (2)
Lizhen Wang (1)
Fei Chen (1)
Runlin Yang (1)
Shineng Luo (1)
Min Yang (1) - 关键词：GLP ; 1R ; Cys39 ; exendin ; 4 ; 18F ; FBEM ; PET imaging ; Insulinoma
- 刊名：Journal of Cancer Research and Clinical Oncology
- 出版年：2014
- 出版时间：September 2014
- 年：2014
- 卷：140
- 期：9
- 页码：1479-1488
- 全文大小：984 KB
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Donghui Pan (1)
Qing Xu (2)
Chen Zhu (2)
Lizhen Wang (1)
Fei Chen (1)
Runlin Yang (1)
Shineng Luo (1)
Min Yang (1)
1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu, China
2. Nanjing Medical University, Nanjing, 210029, Jiangsu, China - ISSN：1432-1335
文摘
Purpose Glucagon-like peptide-1 receptor (GLP-1R) is a specific target for insulinomas imaging since it is overexpressed in the tumor. Exendin-4 exhibits high affinity for the GLP-1R. In this study, a novel 18F-labeled exendin-4 analog, 18F-FBEM–Cys39-exendin-4, was synthesized and its potentials for GLP-1R imaging were also evaluated. Methods 18F-FBEM was synthesized by coupling 18F-fluorobenzoic acid (18F-FBA) with N-(2-aminoethyl) maleimide, and the reaction conditions were optimized. Cys39-exendin-4 was then conjugated with 18F-FBEM to obtain 18F-FBEM–Cys39-exendin-4. The GLP-1R targeting potential and pharmacokinetic profile of the tracer were analyzed in INS-1 insulinoma and MDA-MB-435 breast tumor model, respectively. Results Under the optimal conditions, the yield of radiolabeled 18F-FBEM was 49.1?±?2.0?% (based on 18F-FBA, non-decay corrected). The yield of 18F-FBEM–Cys39-exendin-4 was 35.1?±?2.6?% (based on the starting 18F-FBEM, non-decay corrected). The radiochemical purity of 18F-FBEM–Cys39-exendin-4 is >95?%, and the specific activity was at least 35?GBq/μmol. The GLP-1R-positive INS-1 insulinoma xenograft was clearly visible with good contrast to background, whereas GLP-1R-negative MDA-MB435 breast tumor was barely visible. Low levels of radioactivity were also detected at pancreas and lungs due to few GLP-1R expressions. GLP-1R binding specificity was demonstrated by reduced INS-1 tumor uptake of the tracer after coinjection with an excess of unlabeled Cys39-exendin-4 at 1?h postinjection. Conclusion The thiol-reactive reagent, 18F-FBEM, was prepared with high yield and successfully conjugated to Cys39-exendin-4. Favorable preclinical data showing specific and effective tumor targeting by 18F-FBEM–Cys39-exendin-4 suggest that the tracer may be a potential probe for insulinomas imaging.