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Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe 18F-FBEM–Cys39-exendin-4

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

This work was supported by National Natural Science Foundation (81171399, 81101077), CSC Foundation (2011832173), National Significant New Drugs Creation Program (2012ZX09505-001-001), Jiangsu Province Foundation (BK2011166, BE2012622, BL2012031, BM2012066), Outstanding Professional Fund of Health Ministry in Jiangsu Province (RC2011095), China Postdoctoral Science Foundation of China (No. 2013M531389), and Jiangsu Province Postdoctoral Science Foundation (No. 1301165C).

Conflict of interest

The authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Insulinoma Imaging with Glucagon-Like Peptide-1 Receptor targeting probe 18F-FBEM–Cys39-exendin-4”.

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Authors and Affiliations

  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

    Yuping Xu, Donghui Pan, Lizhen Wang, Fei Chen, Runlin Yang, Shineng Luo & Min Yang

  2. Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Qing Xu & Chen Zhu

Authors
  1. Yuping Xu
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  2. Donghui Pan
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  3. Qing Xu
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  4. Chen Zhu
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  5. Lizhen Wang
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  6. Fei Chen
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  7. Runlin Yang
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  8. Shineng Luo
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  9. Min Yang
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Correspondence to Min Yang.

Additional information

Yuping Xu and Donghui Pan have equally contributed to this work.

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Xu, Y., Pan, D., Xu, Q. et al. Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe 18F-FBEM–Cys39-exendin-4. J Cancer Res Clin Oncol 140, 1479–1488 (2014). https://doi.org/10.1007/s00432-014-1701-8

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  • DOI: https://doi.org/10.1007/s00432-014-1701-8

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