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

Min, Jung‐Joon; Kim, Hyun-Ju; Park, Jae Hyo; Moon, Sungmin; Jeong, Jae-Ho; Hong, Yeoung-Jin; Cho, Kyoung-Oh; Nam, Jong Hee; Kim, Nacksung; Park, Young-Kyu; Bom, Hee‐Seung; Rhee, Joon Haeng; Choy, Hyon E.

doi:10.1007/s11307-007-0120-5

Cited by 94 publications

(100 citation statements)

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“…A model organism, E. coli K12 MG1655, has been demonstrated to specifically colonize a wide array of tumor xenografts, including metastases, following IV administration. 68,69 This has also been supported by findings with other bacterial species such as bifidobacteria. 38 The use of co-imaging techniques to simultaneously visualize luciferase and lux signals in vivo has been used to great effect to demonstrate the clustered growth pattern of lux expressing bacteria in different tumor models 9 (see Figure 4).…”

Section: Instrumentation For Oisupporting

confidence: 65%

“…For example, strains of E. coli rendered metabolically dependent on diaminopimelic acid (DPI) have been generated, permitting maintenance of plasmids featuring DPI-producing genes as plasmid loss lead to bacterial cell death. 68,69 Transposon, 46,70 transducing bacteriophages, 42 temperature sensitive vectors 71 and bacteriophage integrase systems [72][73][74] have been developed to integrate genes into the chromosomes of selected bacteria. However, it is important to stress that the maintenance and expression of high levels of recombinant DNA may place an unwelcome metabolic burden microorganisms.…”

Section: Instrumentation For Oimentioning

confidence: 99%

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Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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Section: Instrumentation For Oisupporting

confidence: 65%

Section: Instrumentation For Oimentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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“…Since the number of bacteria that enter the tumor is a small fraction of the injected dose, variations in the number of injected bacteria between mice can result in dramatic differences on colony progression. For additional information, see several additional references on bacterial preparation for quantitative in vivo studies 3,4 , While these techniques are highly adaptable to a variety of specific studies, some limitations exist for extending to certain applications. For example, intravenous delivery of high bacterial counts may not be desirable for certain bacteria and/or mouse models due to immunological impact.…”

Section: Discussionmentioning

confidence: 99%

Measuring Growth and Gene Expression Dynamics of Tumor-Targeted <em>S. Typhimurium</em> Bacteria

Danino

Prindle

Hasty

et al. 2013

JoVE

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The goal of these experiments is to generate quantitative time-course data on the growth and gene expression dynamics of attenuated S. typhimurium bacterial colonies growing inside tumors.We generated model xenograft tumors in mice by subcutaneous injection of a human ovarian cancer cell line, OVCAR-8 (NCI DCTD Tumor Repository, Frederick, MD).We transformed attenuated strains of S. typhimurium bacteria (ELH430:SL1344 phoPQ-1 ) with a constitutively expressed luciferase (luxCDABE) plasmid for visualization 2 . These strains specifically colonize tumors while remaining essentially non-virulent to the mouse 1 .Once measurable tumors were established, bacteria were injected intravenously via the tail vein with varying dosage. Tumor-localized, bacterial gene expression was monitored in real time over the course of 60 hours using an in vivo imaging system (IVIS). At each time point, tumors were excised, homogenized, and plated to quantitate bacterial colonies for correlation with gene expression data.Together, this data yields a quantitative measure of the in vivo growth and gene expression dynamics of bacteria growing inside tumors. Video LinkThe video component of this article can be found at

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“…Francis et al [49] constructed a novel Potorhabdus luminescence lux operon by cloning of a Gram-positive ribosome binding site and then generated bioluminescent bacteria labeled with the novel operon, which could be detected noninvasively in vivo. Min et al [50,51] developed a quantitative, noninvasive imaging technique that enables monitoring of bioluminescent bacterial migration in living subjects. Using this technique, studies involving the imaging protocol with luciferase-expressing E. coli were a useful approach for quantitative visualization of labeled bacteria in mouse models with tumor xenograft or metastases.…”

Section: Bacterial Luciferasementioning

confidence: 99%

In Vivo Cell Tracking with Bioluminescence Imaging

Kim

Kalimuthu

Ahn

2014

Nucl Med Mol Imaging

132

122

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Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

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

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

Cited by 94 publications

References 21 publications

Bacterial vectors for imaging and cancer gene therapy: a review

Bacterial vectors for imaging and cancer gene therapy: a review

Measuring Growth and Gene Expression Dynamics of Tumor-Targeted <em>S. Typhimurium</em> Bacteria

In Vivo Cell Tracking with Bioluminescence Imaging

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