Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil

Bettegowda, Chetan; Foss, Catherine A.; Cheong, Ian; Wang, Yuchuan; Díaz, Luis A.; Agrawal, Nishant; Fox, James J.; Dick, James D.; Dang, Long H.; Zhou, Shibin; Kinzler, Kenneth W.; Vogelstein, Bert; Pomper, Martin G.

doi:10.1073/pnas.0408861102

Cited by 122 publications

(116 citation statements)

References 28 publications

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“…It should also be noted that 4T1 xenografts in the absence of bacteria accumulate [ The current study showed the feasibility of noninvasive imaging of bacteria based on the expression of genomic bacterial thymidine kinase. The potential for monitoring patients that have received tumor-colonizing bacteria without the inclusion of an exogenous (e.g., viral) reporter gene has previously been shown (5) and is confirmed here. Imaging should be able to determine whether bacterial tumor colonization has occurred successfully and whether previously undetected metastases or specific organs are colonized by the bacteria.…”

Section: Discussionsupporting

confidence: 54%

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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Section: Discussionsupporting

confidence: 54%

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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“…It could also represent an inherent limitation of [ 18 F]FDG-PET imaging. More-specific PET tracers, such as those measuring lymphoidassociated inflammation (25) or radiopharmaceutical or bioluminescence-based imaging biomarkers that directly label bacteria (5,8,14), are anticipated to provide better real-time information about bacterial burdens. However, unlike PET tracers, methods of directly labeling bacteria are currently limited to in vitro systems or experimentally infected animals.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Pulmonary [ ¹⁸ F]-2-Fluoro-Deoxy- d -Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment

Davis¹,

Nuermberger²,

Um³

et al. 2009

Antimicrob Agents Chemother

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127

141

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Tools for monitoring response to tuberculosis (TB) treatment are time-consuming and resource intensive. Noninvasive biomarkers have the potential to accelerate TB drug development, but to date, little progress has been made in utilizing imaging technologies. Therefore, in this study, we used noninvasive imaging to monitor response to TB treatment. BALB/c and C3HeB/FeJ mice were aerosol infected with Mycobacterium tuberculosis and administered bactericidal (standard and highly active) or bacteriostatic TB drug regimens. Serial pulmonary [18 F]-2-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) was compared with standard microbiologic methods to monitor the response to treatment. [18 F]FDG-PET correctly identified the bactericidal activity of the drug regimens. Imaging required fewer animals; was available in real time, as opposed to having CFU counts 4 weeks later; and could also detect TB relapse in a time frame similar to that of the standard method. Lesion-specific [18 F]FDG-PET activity also broadly correlated with TB treatment in C3HeB/FeJ mice that develop caseating lesions. These studies demonstrate the application of noninvasive imaging to monitor TB treatment response. By reducing animal numbers, these biomarkers will allow costeffective studies of more expensive animal models of TB. Validated markers may also be useful as "point-ofcare" methods to monitor TB treatment in humans.New and shorter drug regimens for tuberculosis (TB) are needed to support global control efforts. However, tools for monitoring TB drug treatment in preclinical studies and clinical trials are time-consuming and resource intensive. For instance, typical phase 3/4 trials entail treating hundreds of patients for at least 6 months and monitoring them for at least 1 year for relapse. Phase 2 studies that monitor patients for 8 weeks for sputum culture conversion are limited because sputum bacterial burdens are not available in real time and do not always correlate closely with overall pulmonary disease. This situation is unlike clinical trials evaluating treatments against human immunodeficiency virus infection, where quantitative viral loads and CD4 counts provide well-validated biomarkers of disease burden and progression of disease, respectively. With the alarming rise of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis infections, which account for up to 20% and 2%, respectively, of the global TB disease burden (6), there is significant interest in the use of validated biomarkers to monitor TB treatment in patients. Since clinical indicators can often be misleading, these biomarkers may allow more rapid identification of patients who relapse or respond poorly to TB treatment. The TB Trials Consortium (TBTC) has expressed an urgent need for development of validated biomarkers for monitoring and detecting relapse during and after TB treatment in patients (29). Several biomarker technologies for monitoring TB treatment are under development, though none utilize imaging technologies (24). A...

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“…Two reports use molecular-genetic imaging to identify cells productively transfected with HSV1-TK in preparation for antitumor gene therapy in patients (23,24). We have previously imaged endogenous TK expression to study combined bacteriolytic therapy in experimental models of colon cancer and bacterial infection in general (25). Herein we have used molecular-genetic imaging to study expression of a gene, EBV-TK, as a surrogate marker for induction of the viral lytic cycle and have similarly been able to avoid the gene transfection step.…”

Section: Discussionmentioning

confidence: 99%

Virus-Associated Tumor Imaging by Induction of Viral Gene Expression

Tanhehco

Chen

et al. 2007

Clinical Cancer Research

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Purpose: EBV and other herpesviruses are associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced in vitro with several chemotherapeutic agents that promote viral lytic induction. The goal of this study is to image EBV-associated tumors by induction of viral TK expression with radiolabeled 2 ¶-fluoro-2 ¶-deoxy-h-D-5-iodouracil-arabinofuranoside (FIAU). Experimental Design: Immunoblot, luciferase reporter assay, and in vitro assay with [

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Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil

Cited by 122 publications

References 28 publications

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

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

Noninvasive Pulmonary [ ¹⁸ F]-2-Fluoro-Deoxy- d -Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment

Virus-Associated Tumor Imaging by Induction of Viral Gene Expression

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Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil

Cited by 122 publications

References 28 publications

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

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

Noninvasive Pulmonary [ 18 F]-2-Fluoro-Deoxy- d -Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment

Virus-Associated Tumor Imaging by Induction of Viral Gene Expression

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Noninvasive Pulmonary [ ¹⁸ F]-2-Fluoro-Deoxy- d -Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug Treatment