title: Non-invasive in vivo imaging of tumor-associated CD133/prominin.
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 great importance.
  
  
  RESULTS
  Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry.
  
  
  CONCLUSIONS
  Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics.
authors.affiliation: Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Chizuko
authors.initials: C
authors.lastname: Tsurumi
authors.forename: Norbert
authors.initials: N
authors.lastname: Esser
authors.forename: Elke
authors.initials: E
authors.lastname: Firat
authors.forename: Simone
authors.initials: S
authors.lastname: Gaedicke
authors.forename: Marie
authors.initials: M
authors.lastname: Follo
authors.forename: Martin
authors.initials: M
authors.lastname: Behe
authors.forename: Ursula
authors.initials: U
authors.lastname: Elsässer-Beile
authors.forename: Anca-Ligia
authors.initials: AL
authors.lastname: Grosu
authors.forename: Ralph
authors.initials: R
authors.lastname: Graeser
authors.forename: Gabriele
authors.initials: G
authors.lastname: Niedermann
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D005910:Glioma / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells; D010455:Peptides / Q000378:metabolism*; D012008:Recurrence
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse