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Noninvasive Real-time Imaging of Tumors and Metastases Using Tumor-targeting Light-emitting Escherichia coli

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Abstract

Purpose

A number of bacteria types are known to preferentially grow in tumors. We have taken advantage of this phenomenon to target luciferase-expressing Escherichia coli to tumors and metastases in mouse models to image them noninvasively.

Methods and Results

After intravenous injection of pLux-expressing E. coli (108 CFU), bioluminescence signals from the bacteria were detected exclusively in tumor tissue after 24 hours. The balanced-lethal host–vector system using the gene encoding aspartate β-semialdehyde dehydrogenase (asd) enabled stable maintenance of the pLux in the tumor-targeting E. coli. This phenomenon of selective tumor targeting and proliferation of E. coli was observed in a diverse range of tumors implanted in nude mice. More importantly, E. coli was capable of targeting both primary tumors and metastases, enabling them to be imaged noninvasively in both nude and immunocompetent mice.

Conclusions

Our results suggest the potential clinical use of this technology for tumor targeting.

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Acknowledgements

This study was supported by a grant from the National R&D Program for Cancer Control (0620330-1), Ministry of Health and Welfare, Republic of Korea. H.E.C. was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST) (No. 2007-04213), J.H.R. by grant no. RTI05-01-01 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE); and H.S.B. by grant no. RTI-04-03-03 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE).

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Authors and Affiliations

  1. Laboratory of In Vivo Molecular Imaging, Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, South Korea

    Jung-Joon Min, Jae Hyo Park, Sungmin Moon & Hee-Seung Bom

  2. Department of Microbiology, Chonnam National University Medical School, Gwangju, South Korea

    Hyun-Ju Kim, Jae Ho Jeong, Yeoung-Jin Hong, Joon Haeng Rhee & Hyon E. Choy

  3. Department of Pathology, Chonnam National University College of Veterinary Medicine, Gwangju, South Korea

    Kyoung-Oh Cho

  4. Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea

    Jong Hee Nam

  5. Department of Pharmacology, Chonnam National University Medical School, Gwangju, South Korea

    Nacksung Kim

  6. Department of Surgery, Chonnam National University Medical School, Gwangju, South Korea

    Young-Kyu Park

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  1. Jung-Joon Min
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  2. Hyun-Ju Kim
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Correspondence to Jung-Joon Min.

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Min, JJ., Kim, HJ., Park, J. et al. Noninvasive Real-time Imaging of Tumors and Metastases Using Tumor-targeting Light-emitting Escherichia coli . Mol Imaging Biol 10, 54–61 (2008). https://doi.org/10.1007/s11307-007-0120-5

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  • DOI: https://doi.org/10.1007/s11307-007-0120-5

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