Non-Invasive In Vivo Imaging of Tumor-Associated CD133Prominin 英文参考文献.docVIP

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Non-Invasive In Vivo Imaging of Tumor-Associated CD133Prominin 英文参考文献.doc

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Non-InvasiveInVivoImagingofTumor-Associated CD133/Prominin ChizukoTsurumi1,NorbertEsser5,ElkeFirat1,SimoneGaedicke1,MarieFollo2,MartinBehe3 ,Ursula Elsa¨sser-Beile4,Anca-LigiaGrosu1,RalphGraeser5,GabrieleNiedermann1* 1Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany, 2Department of Internal Medicine I, University Hospital Freiburg, Freiburg, Germany,3DepartmentofNuclearMedicine,UniversityHospitalFreiburg,Freiburg,Germany,4DepartmentofUrology,UniversityHospitalFreiburg,Freiburg,Germany, 5ProQinaseGmbH,Freiburg,Germany Abstract Background: Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of greatimportance. Methodology/PrincipalFindings:Here,wedescribesuccessfulinvivodetectionofCD133/prominin,acancerstemcellsurface markerforavarietyoftumorentities.TheCD133-specificmonoclonalantibodyAC133.1wasusedforquantitativefluorescence- basedopticalimagingofmousexenograftmodelsbasedonisogenicpairsofCD133positiveandnegativecelllines.Afirstset consistedofwild-typeU251glioblastomacells,whichdonotexpressCD133,andlentivirallytransducedCD133-overexpressing U251cells.AsecondsetmadeuseofHCT116coloncarcinomacells,whichuniformlyexpressCD133atlevelscomparableto primaryglioblastomastemcells,andaCD133-negativeHCT116derivative.Notsurprisingly,visualizationandquantificationof CD133inoverexpressingU251xenograftswassuccessful;moreimportantly,however,significantdifferenceswerealsofoundin matchedHCT116xenograftpairs,despitethelowerCD133expressionlevels.Thebindingofi.v.-injectedAC133.1antibodiesto CD133positive,butnotnegative,tumorcellsisolatedfromxenograftswasconfirmedbyflowcytometry. Conclusions/Significance: Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor- associatedCD133isfeasibleandthatCD133antibody-basedtumortargetingisefficient.Thisshouldfacilitatedev