Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK

Soghomonyan, Surren A; Doubrovin, Mikhail; Pike, Jeremy; Luo, Xiaobo; Ittensohn, Martina; Runyan, Jacob D.; Balatoni, Julius; Finn, Ronald D.; Tjuvajev, Juri Gelovani; Blasberg, Ronald G.; Bermudes, David

doi:10.1038/sj.cgt.7700779

Cited by 78 publications

(49 citation statements)

References 40 publications

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“…The immunoprivileged nature of tumors is thought to contribute to the persistence and tumor-selective growth of the bacteria within the tumor (Bermudes et al, 2001b; Darveau, 1999; Low et al, 1999), including providing partial protection from antibody responses, and thus the effect of neutralizing antibodies against the chimeras within the tumors should also be diminished. Furthermore, targeted proteins delivered systemically have limitations for delivery deep inside of tumors, whereas the bacteria localize even within the necrotic regions and can produce therapeutic proteins directly in situ (Soghomonyan et al, 2005), which could overcome that limitation.…”

Section: Discussionmentioning

confidence: 99%

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Quintero

Carrafa²,

Vincent³

et al. 2016

Biotech & Bioengineering

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Tumor-targeted Salmonella VNP20009 preferentially replicate within tumor tissue and partially suppress tumor growth in murine tumor models. These Salmonella have the ability to locally induce apoptosis when they are in direct contact with cancer cells but they lack significant bystander killing, which may correlate with their overall lack of antitumor activity in human clinical studies. In order to compensate for this deficiency without enhancing overall toxicity, we engineered the bacteria to express epidermal growth factor receptor (EGFR)-targeted cytotoxic proteins that are released into the extracellular milieu. In this study, we demonstrate the ability of the Salmonella strain VNP20009 to produce three different forms of the Pseudomonas exotoxin A (ToxA) chimeric with a tumor growth factor alpha (TGFα) which results in its producing culture supernatants that are cytotoxic and induce apoptosis in EGFR positive cancer cells as measured by the tetrazolium dye reduction, and Rhodamine 123 and JC-10 mitochondrial depolarization assays. In addition, exchange of the ToxA REDLK endoplasmic reticulum retention signal for KDEL and co-expression of the ColE3 lysis protein resulted in an overall increased cytotoxicity compared to the wild type toxin. This approach has the potential to significantly enhance the antitumor activity of VNP20009 while maintaining its previously established safety profile.

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Section: Discussionmentioning

confidence: 99%

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Quintero

Carrafa²,

Vincent³

et al. 2016

Biotech & Bioengineering

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“…The (16). Comparing the Salmonella VNP20009 and EcN data shows that the HSV1-TK -transformed Salmonella accumulate more radiopharmaceutical per viable bacteria than EcN bacteria over the dose ranges that were studied (Fig.…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli Nissle 1917 Facilitates Tumor Detection by Positron Emission Tomography and Optical Imaging

Brader

Stritzker²,

Riedl³

et al. 2008

Clinical Cancer Research

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Purpose: Bacteria-based tumor-targeted therapy is a modality of growing interest in anticancer strategies. Imaging bacteria specifically targeting and replicating within tumors using radiotracer techniques and optical imaging can provide confirmation of successful colonization of malignant tissue. Conclusion: EcN canbe imaged by PET, basedon the expressionof endogenous E. coli thymidine kinase, and this imaging paradigm could be translated to patient studies for the detection of solid tumors. Bioluminescence imaging provides a low-cost alternative to PET imaging in small animals.

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“…Such HSV1-TK-expressing Salmonella VNP20009 have been shown to be imageable by [61]. A recent major advancement in this area is the discovery that endogenous bacterial thymidine kinase can be imaged by similar radiolabeled thymidine analogues in the assessment of bacterial distribution and proliferation [62].…”

Section: Bacterial Imagingmentioning

confidence: 99%

Imaging for Infection: From Visualization of Inflammation to Visualization of Microbes

Ady

Fong²

2014

Surgical Infections

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Background: With the development of high-resolution cross-sectional imaging, anatomic identification of most areas of infection has become routine. Imaging a site of infection allows for diagnosis and treatment. In the past, molecular imaging for infection involved mainly the use of radiolabeled leukocytes for functional targeting at infection sites. With the recent development of functional nuclear imaging, bacterial and viral metabolism can also be imaged directly for potential identification of early infection. Methods: Review of pertinent English-language literature. Results: Cross-sectional imaging is used routinely to identify and treat sources of infection in patients with fever, leukocytosis, or unexplained hemodynamic instability. Although ultrasound is preferred for the identification of biliary or hepatic sepsis, computed tomography (CT) has proved to be accurate for the identification and treatment of intra-abdominal fluid collections and abscesses. Biologic imaging is a non-invasive technique that identifies sites of infection in cases in which no definite abnormality is identified via cross-sectional imaging. This is made possible by imaging the accumulation of radioisotopes that have been attached to white blood cells or glucose. Biologic imaging is useful for the identification of anatomic sites where there is inflammation or high metabolic demand. However, a drawback of biologic imaging is that it is not specific for infection. Techniques that image microbes directly increase the specificity of imaging results significantly and can be used to quantify and track infectious processes. For example, radiolabeling of antimicrobial proteins and antibiotics is one technique that has been demonstrated to identify areas of infection accurately in animals but is not currently being used clinically in humans. With the advent of gene therapy, many researchers are inserting the herpes viral thymidine kinase gene into both viruses and bacteria. This allows for tracking of the infectious process by imaging the accumulation of radiolabeled thymidine analogues. Conclusion: This review summarizes standard imaging for infection as it is currently practiced clinically. We will also explore the promising new methods of microbial imaging that are likely to become standards in clinical care in the near future.

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Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK

Cited by 78 publications

References 40 publications

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

EGFR‐targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells

Escherichia coli Nissle 1917 Facilitates Tumor Detection by Positron Emission Tomography and Optical Imaging

Imaging for Infection: From Visualization of Inflammation to Visualization of Microbes

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