title: Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin α(v)β(3) expression in a syngeneic rat model.
abstract: OBJECTIVE
  Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin α(v)β(3)-directed NIR fluorescence probe.
  
  
  METHODS
  Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 × 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin α(v)β(3)-directed NIR fluorescence probe.
  
  
  RESULTS
  Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group).
  
  
  CONCLUSIONS
  These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin α(v)β(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.
authors.affiliation: Department of Surgery, Leiden University Medical Center, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hutteman
authors.forename: J S D
authors.initials: JS
authors.lastname: Mieog
authors.forename: J R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: J
authors.initials: J
authors.lastname: Dijkstra
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: A M A
authors.initials: AM
authors.lastname: van der Laan
authors.forename: H J
authors.initials: HJ
authors.lastname: Tanke
authors.forename: E L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: I
authors.initials: I
authors.lastname: Que
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: C W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: A L
authors.initials: AL
authors.lastname: Vahrmeijer
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000556:secondary*; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007432:Intraoperative Period; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D039302:Integrin alphaVbeta3