Panitumumab-IRDye800CW for Fluorescence-Guided Surgical Resection of Colorectal Cancer

J Surg Res. 2019 Jul;239:44-51. doi: 10.1016/j.jss.2019.01.065. Epub 2019 Feb 22.

Abstract

Background: Fluorescence-guided surgery (FGS) is a rapidly advancing field that may improve outcomes in several cancer types. Although screening has decreased colorectal cancer (CRC) mortality, it remains a common and often fatal malignancy. In this study, we sought to identify an optical imaging agent for the application of FGS technology to CRC.

Methods: We compared a panitumumab-IRDye800CW conjugate to an IgG-IRDye800CW isotype control. Mice were implanted with one of three CRC cell lines (LS174T, Colo205, and SW948) and imaged with open- and closed-filed fluorescence imaging systems. Fluorescent contrast was quantified by calculating the ratio between tumor and background fluorescence. After 10 d, the mice were sacrificed, and their tumors stained for microscopic imaging.

Results: Panitumumab-IRDye800CW produced significantly greater (P < 0.05) fluorescent contrast in all three cell lines. Average tumor to background ratio was 6.00 versus 2.60 for LS174T, 5.78 versus 2.52 for Colo205, and 4.31 versus 1.70 for SW948. A 1-mg tumor fragment produced significantly greater fluorescent contrast in the Colo205 and SW948 cell lines in the panitumumab-IRDye800CW group. Western blotting for epidermal growth factor receptor (EGFR) and a semiquantitative analysis of EGFR expression noted strong expression in all three cell lines; however, EGFR expression did not directly correlate to tumor to background ratio.

Conclusions: Panitumumab-IRDye800CW produces significantly greater fluorescent contrast than IgG-IRDye800CW in a murine model of CRC and is a suitable agent for the application of FGS technology to CRC.

Keywords: Cancer surgery; Colorectal cancer; Epidermal growth factor receptor; Fluorescence-guided surgery; Gastrointestinal surgery; IRDye800CW; Oncology; Panitumumab.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzenesulfonates / administration & dosage*
  • Cell Line, Tumor
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / chemistry
  • Humans
  • Image Processing, Computer-Assisted
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / chemistry
  • Indoles / administration & dosage*
  • Injections, Intravenous
  • Mice
  • Mice, Nude
  • Optical Imaging / instrumentation
  • Optical Imaging / methods*
  • Panitumumab / administration & dosage*
  • Surgery, Computer-Assisted / instrumentation
  • Surgery, Computer-Assisted / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Benzenesulfonates
  • Fluorescent Dyes
  • IRDye 800CW
  • Immunoconjugates
  • Indoles
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors