Hiroto Nishino1, Hannah M Hollandsworth2, Siamak Amirfakhri2, Yoshihiko Tashiro3, Jun Yamamoto3, Michael A Turner2, Thinzar M Lwin2, Bernhard B Singer4, Robert M Hoffman5, Michael Bouvet6. 1. Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California; AntiCancer, Inc., San Diego, California; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California. 3. Department of Surgery, University of California San Diego, San Diego, California; AntiCancer, Inc., San Diego, California. 4. Institute of Anatomy, Medical Faculty, University of Duisburg-Essen, Essen, Germany. 5. Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California; AntiCancer, Inc., San Diego, California. 6. Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California. Electronic address: mbouvet@ucsd.edu.
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.
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: Eric Suero Molina; Johannes Wölfer; Christian Ewelt; André Ehrhardt; Benjamin Brokinkel; Walter Stummer Journal: J Neurosurg Date: 2017-03-24 Impact factor: 5.115
Authors: Thinzar M Lwin; Michael A Turner; Siamak Amirfakhri; Hiroto Nishino; Robert M Hoffman; Michael Bouvet Journal: Cells Date: 2022-01-12 Impact factor: 6.600