title: Near-infrared fluorescence molecular imaging of ductal carcinoma in situ with CD44v6-specific antibodies in mice: a preclinical study.
abstract: OBJECTIVE
  The purpose of this study was to develop a molecular imaging technique using tracers specific for ductal carcinoma in situ (DCIS) to improve visualization and localization of DCIS during surgery. As CD44v6 is frequently expressed in DCIS, we used near-infrared fluorescently labeled CD44v6-targeting antibodies for detection of DCIS.
  
  
  METHODS
  Mice bearing orthotopically transplanted CD44v6-positive MCF10DCIS DCIS-like tumors and CD44v6-negative MDA-MB-231 control tumors were intravenously injected with IRDye800CW conjugated to CD44v6-specific antibodies or control IgGs. Noninvasive imaging was performed for 8 days postinjection, followed by intraoperative imaging. Antibody accumulation and intratumor distribution were examined.
  
  
  RESULTS
  Maximum accumulation of CD44v6-specific antibodies was obtained 24 h postinjection. Maximum tumor-to-background ratio for MCF10DCIS tumors was 4.5 ± 0.2, compared to 1.4 ± 0.1 (control tumors, p = 0.006), and 1.7 ± 0.1 (control IgG, p = 0.014), for 8 days postinjection. Ex vivo, tumor-to-background ratios were comparable to those obtained by intraoperative imaging.
  
  
  CONCLUSIONS
  We show the applicability of noninvasive and intraoperative optical imaging of DCIS-like lesions in vivo using CD44v6-specific antibodies.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: Vermeulen
authors.forename: Aram S A
authors.initials: AS
authors.lastname: van Brussel
authors.forename: Arthur
authors.initials: A
authors.lastname: Adams
authors.forename: Willem P Th M
authors.initials: WP
authors.lastname: Mali
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Patrick W B
authors.initials: PW
authors.lastname: Derksen
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D005453:Fluorescence; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D007430:Intraoperative Care; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000912:Antibodies, Neoplasm; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors