High resolution in vivo bioluminescent imaging for the study of bacterial tumour targeting

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dc.contributor.authorCronin, Michelle
dc.contributor.authorAkin, Ali R.
dc.contributor.authorCollins, Sara A.
dc.contributor.authorMeganck, Jeff
dc.contributor.authorKim, Jae-Beom
dc.contributor.authorBaban, Chwanrow K.
dc.contributor.authorJoyce, Susan A.
dc.contributor.authorvan Dam, Gooitzen M.
dc.contributor.authorZhang, Ning
dc.contributor.authorvan Sinderen, Douwe
dc.contributor.authorO'Sullivan, Gerald C.
dc.contributor.authorKasahara, Noriyuki
dc.contributor.authorGahan, Cormac G.
dc.contributor.authorFrancis, Kevin P.
dc.contributor.authorTangney, Mark
dc.contributor.editorKarathanasis, Efstathios
dc.contributor.funderEuropean Commissionen
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2012-11-29T11:52:51Z
dc.date.available2012-11-29T11:52:51Z
dc.date.copyright2012
dc.date.issued2012-01-25
dc.description.abstractThe ability to track microbes in real time in vivo 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 lux. 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 (mCT) for interpretation. In this study, the non-pathogenic commensal bacteria E.coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (IV) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux 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 lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and mCT 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. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations.en
dc.description.sponsorshipEuropean Commission (Seventh Framework Programme PIOF-GA-2009-255466); Health Research Board (HRA_POR/2010/138)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCRONIN, M., AKIN, A. R., COLLINS, S. A., MEGANCK, J., KIM, J.-B., BABAN, C. K., JOYCE, S. A., VAN DAM, G. M., ZHANG, N., VAN SINDEREN, D., O'SULLIVAN, G. C., KASAHARA, N., GAHAN, C. G., FRANCIS, K. P. & TANGNEY, M. 2012. High Resolution In Vivo Bioluminescent Imaging for the Study of Bacterial Tumour Targeting. Plos One, 7, e30940. http://dx.doi.org/10.1371%2Fjournal.pone.0030940en
dc.identifier.doi10.1371/journal.pone.0030940
dc.identifier.issn1932-6203
dc.identifier.issued1en
dc.identifier.journaltitlePLoS Oneen
dc.identifier.startpagee30940en
dc.identifier.urihttps://hdl.handle.net/10468/822
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030940
dc.rights© 2012 Cronin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en
dc.subjectBioluminescent imaging (BLI)en
dc.subjectTumouren
dc.subjectMicro-computed tomographyen
dc.subjectE.coli K-12 MG1655en
dc.subjectBifidobacterium breve UCC2003en
dc.subjectSalmonella typhimurium SL7207en
dc.subjectluxABCDE operonen
dc.subjectin vivoen
dc.titleHigh resolution in vivo bioluminescent imaging for the study of bacterial tumour targetingen
dc.typeArticle (peer-reviewed)en
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