A Novel Color-Coded Liver Metastasis Mouse Model to Distinguish Tumor and Adjacent Liver Segment.

Abstract

BACKGROUND:

It is difficult to distinguish between a tumor and its liver segment with traditional use of indocyanine green (ICG) alone. In the present study, a method was used to limit ICG to the liver segment adjacent to a tumor. A spectrally-distinct fluorescently-labeled tumor-specific antibody against human carcinoembryonic antigen-related cell-adhesion molecules was used to label the metastatic tumor in a patient-derived orthotopic xenograft mouse model to enable color-coded visualization and distinction of a colon-cancer liver metastases and its adjacent liver segment.

MATERIALS AND METHODS:

Nude mice received surgical orthotopic implantation in the liver of colon-cancer liver metastases derived from two patients. An anti- carcinoembryonic antigen-related cell-adhesion molecules monoclonal antibody (mAb 6G5j) was conjugated to a near-infrared dye IR700DX (6G5j-IR700DX). After three weeks, mice received 6G5j-IR700DX via tail-vein injection 48 hours before surgery. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in labeling of the segment with preserved blood-flow in the liver. Imaging was performed with the Pearl Trilogy and FLARE Imaging Systems.

RESULTS:

The metastatic liver tumor had a clear fluorescence signal due to selective tumor targeting by 6G5j-IR700DX, which was imaged on the 700 nm channel. The adjacent liver segment, with preserved blood-flow in the liver, had a clear fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor fluorescing at 700 nm and the adjacent liver segment fluorescing at 800 nm.

CONCLUSIONS:

Color-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.

• Authors: Hiroto Nishino, Hannah M Hollandsworth, Siamak Amirfakhri, Yoshihiko Tashiro, Jun Yamamoto, Michael A Turner, Thinzar M Lwin, Bernhard B Singer, Robert M Hoffman, Michael Bouvet
• Journal: The Journal of surgical research (J Surg Res) Vol. 264 Pg. 327-333 (08 2021) ISSN: 1095-8673 [Electronic] United States
• PMID: 33848831 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• CEACAM5 protein, human
• Carcinoembryonic Antigen
• Fluorescent Dyes
• GPI-Linked Proteins
• Indocyanine Green

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Carcinoembryonic Antigen (metabolism)
• Colonic Neoplasms (pathology)
• Color
• Fluorescent Dyes (administration & dosage)
• GPI-Linked Proteins (metabolism)
• Hepatectomy (methods)
• Humans
• Indocyanine Green (administration & dosage)
• Injections, Intravenous
• Liver (diagnostic imaging, pathology, surgery)
• Liver Neoplasms (diagnosis, secondary, surgery)
• Mice
• Molecular Imaging (methods)
• Optical Imaging (methods)
• Xenograft Model Antitumor Assays