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Synthesis of a Novel l-Methyl-Methionine–ICG-Der-02 Fluorescent Probe for In Vivo Near Infrared Imaging of Tumors

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Abstract

Purpose

A novel near infrared fluorescent probe, l-methyl-methionine (Met)–ICG-Der-02, was synthesized and characterized for in vivo imaging of tumors and early diagnosis of cancers.

Method

Met was conjugated with ICG-Der-02 dye through the amide bond function by ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide catalysis chemistry. Met–ICG-Der-02 probe uptake was evaluated on PC3, MDA-MB-231, and human embryonic lung fibroblast cell lines. The dynamics of Met–ICG-Der-02 was investigated in athymic nude mice prior to evaluation of the probe targeting capability in prostate and breast cancer models.

Results

Met–ICG-Der-02 was successfully synthesized. Cell experiments demonstrated excellent cellular uptake of Met–ICG-Der-02 on cancer cell lines without cytotoxicity. Optical imaging showed a distinguishable fluorescence signal in the tumor area at 2 h while maximal tumor-to-normal tissue contrast ratio was at 12 h Met–ICG-Der-02 post-injection. Additionally, dynamic study of the probe indicated intestinal and liver–kidney clearance pathways.

Conclusion

Met–ICG-Der-02 probe is a promising optical imaging agent for tumor diagnosis, especially in their early stage.

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Acknowledgments

The authors are grateful to Natural Science Foundation Committee of China (NSFC30672015, NSFC30700779, NSFC30800257, NSFC30970776, NSFC81000666, NSFC31050110123, NSFC81071194, and NSFC81171395) and the Ministry of Science and Technology (2009ZX09310-004) for their financial supports.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China

    Didel M. Mahounga, Lingling Shan, Cao Jie, Changli Du, Shunan Wan & Yueqing Gu

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  1. Didel M. Mahounga
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  2. Lingling Shan
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  3. Cao Jie
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  4. Changli Du
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  5. Shunan Wan
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  6. Yueqing Gu
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Correspondence to Yueqing Gu.

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Mahounga, D.M., Shan, L., Jie, C. et al. Synthesis of a Novel l-Methyl-Methionine–ICG-Der-02 Fluorescent Probe for In Vivo Near Infrared Imaging of Tumors. Mol Imaging Biol 14, 699–707 (2012). https://doi.org/10.1007/s11307-012-0560-4

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  • DOI: https://doi.org/10.1007/s11307-012-0560-4

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