1. A Novel Color-Coded Liver Metastasis Mouse Model to Distinguish Tumor and Adjacent Liver Segment
- Author
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Nishino, Hiroto, Hollandsworth, Hannah M, Amirfakhri, Siamak, Tashiro, Yoshihiko, Yamamoto, Jun, Turner, Michael A, Lwin, Thinzar M, Singer, Bernhard B, Hoffman, Robert M, and Bouvet, Michael
- Subjects
Liver Disease ,Biotechnology ,Colo-Rectal Cancer ,Digestive Diseases ,Cancer ,Animals ,Antibodies ,Monoclonal ,Carcinoembryonic Antigen ,Colonic Neoplasms ,Color ,Fluorescent Dyes ,GPI-Linked Proteins ,Hepatectomy ,Humans ,Indocyanine Green ,Injections ,Intravenous ,Liver ,Liver Neoplasms ,Mice ,Molecular Imaging ,Optical Imaging ,Xenograft Model Antitumor Assays ,Liver metastases ,Colon cancer ,Nude mouse model ,Indocyanine green ,Fluorescent tumor-specific antibody ,CEACAM ,Color-coded fluorescence imaging ,Clinical Sciences ,Surgery - Abstract
BackgroundIt 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 methodsNude 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.ResultsThe 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.ConclusionsColor-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.
- Published
- 2021