High Resolution In Vivo Bioluminescent Imaging for the Study of Bacterial Tumour Targeting
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Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and μCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/350907", "https://ndownloader.figshare.com/files/350968", "https://ndownloader.figshare.com/files/350998", "https://ndownloader.figshare.com/files/351037"], "description"=>"<div><p>The ability to track microbes in real time <em>in vivo</em> is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as <em>lux</em>. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation.</p> <p>In this study, the non-pathogenic commensal bacteria <em>E.coli</em> K-12 MG1655 and <em>Bifidobacterium breve</em> UCC2003, or <em>Salmonella</em> Typhimurium SL7207 each expressing the <em>luxABCDE</em> operon were intravenously (IV) administered to mice bearing subcutaneous (s.c) <em>FLuc</em>-expressing xenograft tumours. Bacterial <em>lux</em> signal was detected specifically in tumours of mice post IV-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both <em>lux</em> and <em>FLuc</em>, bacteria and tumour cells were co-localised. 3D BLI and μCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by <em>ex vivo</em> histological analyses. <em>In vivo</em> imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally <em>in vivo</em> using approaches that provide unique information on spatial locations.</p> </div>", "links"=>[], "tags"=>["bioluminescent", "imaging", "bacterial", "tumour", "targeting"], "article_id"=>129357, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0030940.s001", "https://dx.doi.org/10.1371/journal.pone.0030940.s002", "https://dx.doi.org/10.1371/journal.pone.0030940.s003", "https://dx.doi.org/10.1371/journal.pone.0030940.s004"], "stats"=>{"downloads"=>7, "page_views"=>46, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/High_Resolution_In_Vivo_Bioluminescent_Imaging_for_the_Study_of_Bacterial_Tumour_Targeting/129357", "title"=>"High Resolution <em>In Vivo</em> Bioluminescent Imaging for the Study of Bacterial Tumour Targeting", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-01-25 02:35:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/688954"], "description"=>"<p>(<b>a</b>) <b>Whole Body 3D co-registration of lux, FLuc and μCT.</b> Combined luminescence and μCT demonstrating co-localisation of <i>B. breve</i> (bacterial lux - orange) and subcutaneous HCT116-luc2 tumour (FLuc - green). (<b>b</b>) <b>Intratumoural Imaging.</b> Combined μCT and luminescence imaging. Magnification of subcutaneous tumour from mouse in (a), top, side and base view. Viable tumour (FLuc green/blue), vasculature (contrast agent – red) and bacterial (orange/yellow) signals are visualised. Movie on website (Movie S3).</p>", "links"=>[], "tags"=>["microbiology", "oncology", "Biochemistry"], "article_id"=>359428, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_registration_with_956_CT_/359428", "title"=>"Co-registration with μCT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:37:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/688318"], "description"=>"<p>(<b>a,b</b>) Bioluminescence from <i>B. breve</i> UCC2003, <i>E. coli</i> MG1655 or <i>S.</i> Typhimurium SL7207 in s.c. LLC tumour bearing mice 11 days following IV delivery. Representative mice are shown. Increase in bacterial bioluminescence in tumours was observed over time (n = 6). Data graphed represent the mean ± S.E. There was no detectable bioluminescence in organs of treated animals, except for <i>S.</i> Typhimurium (<b>c</b>) Representative <i>S.</i> Typhimurium administered mice displaying non-tumour-specific bacterial bioluminescence. Ventral image – Day 3, Dorsal – Day 11. (<b>d</b>) All tumour types examined were colonised by the various strains. (i) <i>B. breve</i>, B16, Day 11 (ii) <i>E. coli</i>, FaDu, Day 7 (iii) <i>B. breve</i>, U87, Day 14.</p>", "links"=>[], "tags"=>["microbiology", "oncology", "Biochemistry"], "article_id"=>358788, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bacterial_Growth_in_Tumours_/358788", "title"=>"Bacterial Growth in Tumours.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:26:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/688828"], "description"=>"<p>Fluorescent bacterial and tumour cells were imaged using fluorescence microscopy (Nuance). Blue- DAPI (nuclei), Green- U87/GFP, Magenta- <i>B. breve</i>/pCheMC.</p>", "links"=>[], "tags"=>["histological"], "article_id"=>359307, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ex_vivo_histological_analysis_/359307", "title"=>"<i>Ex vivo</i> histological analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:35:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/688450"], "description"=>"<p>Viable bacteria in tumours were enumerated by <i>ex vivo</i> bacterial culture from LLC tumours subsequent to BLI at various time-points post IV administration of <i>B. breve</i> or <i>E. coli</i> (n = 6). (<b>a</b>) <b>Bacterial replication in tumours.</b> Increases over time in viable bacterial numbers and bioluminescence. Data graphed represent the mean ± S.E. (<b>b</b>) <b>Correlation between bacterial numbers and bioluminescence in tumours.</b> Direct comparison between photon flux and bacterial colony counts. Log values of bacterial numbers relative to <i>in vivo</i> bioluminescent units are graphed. Correlation between bacterial counts and bacterial bioluminescence signals: R<sup>2</sup> = 0.84 for <i>B. breve</i>: R<sup>2</sup> = 0.97 for <i>E. coli</i> which correlates well with previous studies using <i>E. coli</i> MG1655 where R<sup>2</sup> = 0.94, <i>P</i><0.001 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030940#pone.0030940-Min1\" target=\"_blank\">[57]</a>.</p>", "links"=>[], "tags"=>["bacterial", "numbers"], "article_id"=>358922, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relationship_Between_Bacterial_Numbers_And_Bioluminescence_/358922", "title"=>"Relationship Between Bacterial Numbers And Bioluminescence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:28:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/688553"], "description"=>"<p>The GIT of mice was colonised with either <i>B. breve</i> or <i>E. coli</i> by oral administration of 10<sup>9</sup> cfu of the relevant strain for three consecutive days. (<b>a</b>) 2D image of athymic mouse 9 days post final feed with <i>B. breve</i> UCC2003/lux. (<b>b</b>) IVIS XR 2D bioluminescence overlayed with X-ray image of mouse 27 days-post feeding with <i>E. coli</i> MG1655/lux. (<b>c</b>) Bacterial counts in specific regions of the GIT 14 days post feeding. Abdominal bioluminescence corresponding to average cfu is also shown (black dots). Data graphed represent the mean ± S.E. (<b>d</b>) Sample isolated images from 3D tomography of mouse from (b). 3D images show a digital mouse atlas of the skeleton to provide anatomical registration. (Movie available in Movie S1). <i>E. coli</i> MG1655 bioluminescence is visible in blue at lower, and white or green at higher levels.</p>", "links"=>[], "tags"=>["bioluminescence"], "article_id"=>359031, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bacterial_Bioluminescence_in_the_GIT_/359031", "title"=>"Bacterial Bioluminescence in the GIT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:30:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/688667"], "description"=>"<p>(<b>a</b>) <b>2D bioluminescence co-registration.</b> Athymic mouse bearing s.c. FLuc expressing FaDu tumour 7 days post IV administration of <i>B. breve</i>. Tumour FLuc = Green, Bacterial lux = orange. (<b>b</b>) <b>3D bioluminescence co-registration.</b> 3D overlay of <i>B. breve</i> lux (orange) 10 days post administration to athymic mice bearing HCT116 FLuc (green) expressing tumours.</p>", "links"=>[], "tags"=>["tumour", "bacterial"], "article_id"=>359140, "categories"=>["Cancer", "Biochemistry", "Microbiology"], "users"=>["Michelle Cronin", "Ali R. Akin", "Sara A. Collins", "Jeff Meganck", "Jae-Beom Kim", "Chwanrow K. Baban", "Susan A. Joyce", "Gooitzen M. van Dam", "Ning Zhang", "Douwe van Sinderen", "Gerald C. O'Sullivan", "Noriyuki Kasahara", "Cormac G. Gahan", "Kevin P. Francis", "Mark Tangney"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0030940.g004", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_localisation_of_Tumour_And_Bacterial_Bioluminescence_/359140", "title"=>"Co-localisation of Tumour And Bacterial Bioluminescence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-01-25 02:32:20"}

PMC Usage Stats | Further Information

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Relative Metric

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