Visualizing Implanted Tumors in Mice with Magnetic Resonance Imaging Using Magnetotactic Bacteria

Benoit, M; Mayer, Dirk; Barak, Yoram; Chen, Ian Y.; Hu, Weixu; Cheng, Zhen; Wang, Shan X.; Spielman, Daniel M.; Gambhir, Sanjiv S.; Матин, А.

doi:10.1158/1078-0432.ccr-08-3206

Cited by 107 publications

(82 citation statements)

References 33 publications

(30 reference statements)

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“…100 A drawback is its low sensitivity: approximately micromolar concentrations of an imaging probe can be detected within a given voxel (10 À 3 -10 À 5 mol/l) which is three to six orders of magnitude lower than the sensitivity of optical imaging for detection of fluorochromes in vivo. 101 Benoit et al 102 exploited the innate physiology of magnetotactic bacteria to target tumors in mice and provide positive contrast for visualization using MRI. The ability of Magnetospirillum magneticum AMB-1 to confer positive MRI contrast was determined both in vitro and in vivo.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…The ability of Magnetospirillum magneticum AMB-1 to confer positive MRI contrast was determined both in vitro and in vivo. 102 The strain was administered to tumor bearing mice either intra-tumorally or intravenously and tumor targeting was confirmed using a multiple of approaches including 64 Cu-labeled bacteria. Significantly M. magneticum with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by MRI.…”

Section: Magnetic Resonance Imagingmentioning

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: Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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“…In addition to synthetic iron oxide nanoparticles, the use of magnetosomes (MNs) in biomedicine has also been recently proposed (8,9). These nanostructures, constituted by pure magnetite particles arranged in chains and surrounded by a phospholipid membrane (10,11), are naturally synthesized by magnetotactic bacteria under specific environmental conditions.…”

Section: Introductionmentioning

confidence: 99%

Characterization of magnetic nanoparticles from Magnetospirillum Gryphiswaldense as potential theranostics tools

Orlando

Mannucci

Fantechi

et al. 2015

Contrast Media & Molecular

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We investigated the theranostic properties of magnetosomes (MNs) extracted from magnetotactic bacteria, promising for nanomedicine applications. Besides a physico-chemical characterization, their potentiality as mediators for magnetic fluid hyperthermia and contrast agents for magnetic resonance imaging, both in vitro and in vivo, are here singled out. The MNs, constituted by magnetite nanocrystals arranged in chains, show a superparamagnetic behaviour and a clear evidence of Verwey transition, as signature of magnetite presence. The phospholipid membrane provides a good protection against oxidation and the MNs oxidation state is stable over months. Using an alternate magnetic field, the specific absorption rate was measured, resulting among the highest reported in literature. The MRI contrast efficiency was evaluated by means of the acquisition of complete NMRD profiles. The transverse relaxivity resulted as high as the one of a former commercial contrast agent. The MNs were inoculated into an animal model of tumour and their presence was detected by magnetic resonance images two weeks after the injection in the tumour mass.

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“…Benoit et al reported that the magnetotactic bacteria Magnetospirillum magneticum AMB-1 could produce positive MRI contrast and colonize mouse tumor xenografts, providing a potential tool for MRI visualization of bacteria in preclinical and translational studies to track cancer despite its lower sensitivity. Following IV injection of 64 Cu-labeled AMB-1, PET imaging also revealed increased bacterial colonization of tumors, but decreased colonization of other organs, such as liver and spleen, after 4 h [57].…”

Section: Bacteriamentioning

confidence: 99%

Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

Min

Nguyen

Gambhir

2010

Nucl Med Mol Imaging

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Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

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Visualizing Implanted Tumors in Mice with Magnetic Resonance Imaging Using Magnetotactic Bacteria

Cited by 107 publications

References 33 publications

Bacterial vectors for imaging and cancer gene therapy: a review

Bacterial vectors for imaging and cancer gene therapy: a review

Characterization of magnetic nanoparticles from Magnetospirillum Gryphiswaldense as potential theranostics tools

Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

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