Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery

Carlos H F Chan; Lukas F Liesenfeld; Isabel Ferreiro-Neira; James C Cusack Jr

doi:10.1245/s10434-016-5690-5

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Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery

Journal article

Peer reviewed

Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery

Carlos H F Chan, Lukas F Liesenfeld, Isabel Ferreiro-Neira and James C Cusack Jr

Annals of surgical oncology, Vol.24(4), pp.931-938

04/2017

DOI: 10.1245/s10434-016-5690-5

PMID: 27913947

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Abstract

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. 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. 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. 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.

Immunohistochemistry

Fluorescence

Neoplasm Transplantation

Humans

Middle Aged

Male

Cytoreduction Surgical Procedures

Peritoneal Neoplasms - chemistry

Optical Imaging - instrumentation

Hyperthermia, Induced

Adult

Female

Optical Imaging - methods

Cathepsins - analysis

Peritoneal Neoplasms - secondary

HCT116 Cells

Reverse Transcriptase Polymerase Chain Reaction

Cathepsin B - analysis

HT29 Cells

Animals

Cathepsins - genetics

Peritoneal Neoplasms - diagnostic imaging

Aged

Appendiceal Neoplasms - pathology

Mice

Colorectal Neoplasms - pathology

Peritoneal Neoplasms - therapy

Preoperative Period

Details

Title: Subtitle: Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery
Creators: Carlos H F Chan - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA. carloshfchan@gmail.com
Lukas F Liesenfeld - Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
Isabel Ferreiro-Neira - Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
James C Cusack Jr - Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. jcusack@mgh.harvard.edu
Resource Type: Journal article
Publication Details: Annals of surgical oncology, Vol.24(4), pp.931-938
Publisher: United States
DOI: 10.1245/s10434-016-5690-5
PMID: 27913947
ISSN: 1068-9265
eISSN: 1534-4681
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 04/2017
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984047862902771

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