title: Intraoperative fluorescence imaging of peritoneal dissemination of ovarian carcinomas. A preclinical study.
abstract: OBJECTIVE
  Improvement of the management and outcome of ovarian cancers may require intraoperative detection and therapeutic intervention to treat minimal residual disease after complete surgery. The aim of this study was to validate the importance of fluorescence in the peroperative detection of human ovarian adenocarcinoma cells and to determine its efficiency in detecting infra millimetric tumor metastases.
  
  
  METHODS
  A fluorescent RAFT-(cRGD)₄ tracer molecule (AngioStamp®) was used. The tracer is based on a biomarker, which has a very high affinity for the α(v)β₃ integrin, which is overexpressed in a large ratio of cancer cells and neovessel endothelial cells during angiogenesis. Infrared fluorescence was visualized with Fluobeam®, an open fluorescent imaging system that could potentially be used in peroperative conditions in the future.
  
  
  RESULTS
  This novel technique allowed the specific detection of residual tumor deposits and inframillimetric metastases, smaller than 500μm, which were resected under fluorescent guidance. AngioStamp® was able to detect all types of cell lines, derived from human ovarian adenocarcinomas, before or after chemotherapy treatment in animals. The effectiveness of AngioStamp® for the detection of various human ovarian adenocarcinomas was assessed on 10 different fragments of tumor, implanted subcutaneously in nude mice. All implanted tumor fragments were visualized by AngioStamp®.
  
  
  CONCLUSIONS
  The high rate of recurrence after apparently complete surgery and/or complete clinical response to chemotherapy implies that most patients have undetected minimal residual disease. Novel techniques such as laparoscopic or laparotomic fluorescence may prove to be crucial in reassessing the definition of primary outcome in ovarian cancer management.
authors.affiliation: Institut Claudius Regaud, EA3035, Toulouse, F-31052, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Mery
authors.forename: Eva
authors.initials: E
authors.lastname: Jouve
authors.forename: Stephanie
authors.initials: S
authors.lastname: Guillermet
authors.forename: Maxime
authors.initials: M
authors.lastname: Bourgognon
authors.forename: Magali
authors.initials: M
authors.lastname: Castells
authors.forename: Muriel
authors.initials: M
authors.lastname: Golzio
authors.forename: Philippe
authors.initials: P
authors.lastname: Rizo
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Delord
authors.forename: Denis
authors.initials: D
authors.lastname: Querleu
authors.forename: Bettina
authors.initials: B
authors.lastname: Couderc
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery; D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005260:Female; D005453:Fluorescence; D006801:Humans; D007432:Intraoperative Period; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D018365:Neoplasm, Residual; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000601:surgery*; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000601:surgery*; D014183:Transplantation, Heterologous