title: Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery.
abstract: BACKGROUND
  Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis.
  
  
  METHODS
  Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis. Expression of different cathepsins (CTS-B, -D, -F, -G, -K, -L, -O, and -S) was determined by quantitative RT-PCR and immunohistochemistry. The hand-held cathepsin-based fluorescent imaging system was used to detect peritoneal xenografts derived from human colon cancer cells (HT29, LoVo and HCT116) in nu/nu mice.
  
  
  RESULTS
  While the expression levels of CTS-B, -D, -L, and -S could be higher in peritoneal tumors than normal peritoneum with a median (range) of 6.1 (2.9-25.8), 2.0 (1.0-15.8), 1.4 (0.8-7.0), and 2.1 (1.6-13.9) folds by quantitative RT-PCR, respectively, CTS-B was consistently the major contributor of the overall cathepsin expression in appendiceal and colonic peritoneal tumors, including adenocarcinomas and low-grade appendiceal mucinous neoplasms. Using peritoneal xenograft mouse models, small barely visible colonic peritoneal tumors (<2.5 mm in maximum diameter) could be detected by the hand-held cathepsin-based fluorescent imaging system.
  
  
  CONCLUSIONS
  Because cathepsin expression is higher in peritoneal tumors than underlying peritoneum, the hand-held cathepsin-based fluorescent imaging system could be useful for intraoperative detection of microscopic peritoneal metastasis during CRS-HIPEC and clinical trial is warranted.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. carloshfchan@gmail.com.|Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA. carloshfchan@gmail.com.
authors.forename: Carlos H F
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Lukas F
authors.initials: LF
authors.lastname: Liesenfeld
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreiro-Neira
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. jcusack@mgh.harvard.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Cusack
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001063:Appendiceal Neoplasms / Q000473:pathology*; D002401:Cathepsin B / Q000032:analysis; D002403:Cathepsins / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000473:pathology*; D065426:Cytoreduction Surgical Procedures; D005260:Female; D005453:Fluorescence; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D061848:Optical Imaging / Q000295:instrumentation* / Q000379:methods; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000556:secondary / Q000628:therapy*; D057234:Preoperative Period; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002403:Cathepsins; D002401:Cathepsin B