Proof of concept of improved fluorescence-guided surgery of colon cancer liver metastasis using color-coded imaging of a tumor-labeling fluorescent antibody and indocyanine green restricted to the adjacent liver segment

Published:August 01, 2022DOI:



      Indocyanine green has been used for fluorescence-guided surgery of liver metastasis and labeling of liver segments. However, indocyanine green is nonspecific, and indocyanine green labeling does not always clearly outline tumor margins. In addition, it is difficult to distinguish between a tumor and its adjacent liver segment colored with indocyanine green alone. In the present study, we performed fluorescence-guided surgery in an orthotopic colon-cancer liver metastasis mouse model by labeling the metastatic liver tumor with an anti-carcinoembryonic antigen fluorescent antibody and with indocyanine green restricted to the adjacent liver segment.


      A liver metastasis model was established with human LS174T colon cancer tumor fragments. To label the tumor, mice received SGM-101, an anti-carcinoembryonic antigen antibody conjugated to a near-infrared fluorophore (700 nm), currently in clinical trials, 3 days before surgery. Indocyanine green (800 nm) was injected after ligation of the tumor-bearing Glissonean pedicle with fluorescence labeling restricted to the liver segment adjacent to the tumor. Bright-light surgery and fluorescence-guided surgery were performed to resect the liver metastasis. To assess recurrence, mice underwent necropsy 3 weeks after surgery and the tumor was weighed.


      Fluorescence-guided anatomic left lateral lobectomy and fluorescence-guided partial liver resection were both performed with color-coded double labeled imaging. Tumor weight 3 weeks after surgery was significantly lower with fluorescence-guided surgery compared to bright-light surgery (38 ± 57 mg vs 836 ± 668 mg, P = .011) for partial liver resection.


      The present study provides a proof-of-concept that color-coded and double labeling of the tumor and adjacent liver segment has the potential to improve liver metastasectomy.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Adam R.
        • De Gramont A.
        • Figueras J.
        • et al.
        The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus.
        Oncologist. 2012; 17: 1225-1239
        • Makuuchi M.
        • Hasegawa H.
        • Yamazaki S.
        Ultrasonically guided subsegmentectomy.
        Surg Gynecol Obstet. 1985; 161: 346-350
        • Hamady Z.Z.
        • Lodge J.P.
        • Welsh F.K.
        • et al.
        One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.
        Ann Surg. 2014; 259: 543-548
        • Hasegawa K.
        • Kokudo N.
        • Imamura H.
        • et al.
        Prognostic impact of anatomic resection for hepatocellular carcinoma.
        Ann Surg. 2005; 242: 252-259
        • Mise Y.
        • Aloia T.A.
        • Brudvik K.W.
        • et al.
        Parenchymal-sparing hepatectomy in colorectal liver metastasis improves salvageability and survival.
        Ann Surg. 2016; 263: 146-152
        • Wang X.
        • Teh C.S.C.
        • Ishizawa T.
        • et al.
        Consensus guidelines for the use of fluorescence imaging in hepatobiliary surgery.
        Ann Surg. 2021; 274: 97-106
        • Lwin T.M.
        • Hoffman R.M.
        • Bouvet M.
        Fluorescence-guided hepatobiliary surgery with long and short wavelength fluorophores.
        Hepatobiliary Surg Nutr. 2020; 9: 615-639
        • Wakabayashi T.
        • Cacciaguerra A.B.
        • Abe Y.
        • et al.
        Indocyanine green fluorescence navigation in liver surgery: a systematic review on dose and timing of administration.
        Ann Surg. 2022; 275: 1025-1034
        • Ishizawa T.
        • Fukushima N.
        • Shibahara J.
        • et al.
        Real-time identification of liver cancers by using indocyanine green fluorescent imaging.
        Cancer. 2009; 115: 2491-2504
        • Aoki T.
        • Yasuda D.
        • Shimizu Y.
        • et al.
        Image-guided liver mapping using fluorescence navigation system with indocyanine green for anatomical hepatic resection.
        World J Surg. 2008; 32: 1763-1767
        • Nishino H.
        • Hatano E.
        • Seo S.
        • et al.
        Real-time navigation for liver surgery using projection mapping with indocyanine green fluorescence: development of the novel medical imaging projection system.
        Ann Surg. 2018; 267: 1134-1140
        • Vauthey J.N.
        • Chaoui A.
        • Do K.A.
        • et al.
        Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.
        Surgery. 2000; 127: 512-519
        • Clavien P.A.
        • Petrowsky H.
        • DeOliveira M.L.
        • Graf R.
        Strategies for safer liver surgery and partial liver transplantation.
        N Engl J Med. 2007; 356: 1545-1559
        • Nishino H.
        • Hollandsworth H.M.
        • Amirfakhri S.
        • et al.
        A novel color-coded liver metastasis mouse model to distinguish tumor and adjacent liver segment.
        J Surg Res. 2021; 264: 327-333
        • Gutowski M.
        • Framery B.
        • Boonstra M.C.
        • et al.
        SGM-101: an innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery.
        Surg Oncol. 2017; 26: 153-162
        • Boogerd L.S.F.
        • Hoogstins C.E.S.
        • Schaap D.P.
        • et al.
        Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study.
        Lancet Gastroenterol Hepatol. 2018; 3: 181-191
        • Schaap D.P.
        • de Valk K.S.
        • Deken M.M.
        • et al.
        Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer.
        Br J Surg. 2020; 107: 334-337
        • Tiernan J.P.
        • Perry S.L.
        • Verghese E.T.
        • et al.
        Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting.
        Br J Cancer. 2013; 108: 662-667
        • Meijer R.P.J.
        • de Valk K.S.
        • Deken M.M.
        • et al.
        Intraoperative detection of colorectal and pancreatic liver metastases using SGM-101, a fluorescent antibody targeting CEA.
        Eur J Surg Oncol. 2021; 47: 667-673
        • Nishino H.
        • Hollandsworth H.M.
        • Sugisawa N.
        • et al.
        Sutureless surgical orthotopic implantation technique of primary and metastatic cancer in the liver of mouse models.
        Vivo. 2020; 34: 3153-3157
        • Framery B.
        • Gutowski M.
        • Dumas K.
        • et al.
        Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients.
        Toxicol Rep. 2019; 6: 409-415
        • Nishino H.
        • Hollandsworth H.M.
        • Tashiro Y.
        • et al.
        Ligation method to specifically label a liver segment with indocyanine green in an orthotopic nude-mouse liver-metastasis model.
        Vivo. 2020; 34: 3159-3162
        • Ishizawa T.
        • Saiura A.
        • Kokudo N.
        Clinical application of indocyanine green-fluorescence imaging during hepatectomy.
        Hepatobiliary Surg Nutr. 2016; 5: 322-328
        • Masuda K.
        • Kaneko J.
        • Kawaguchi Y.
        • et al.
        Diagnostic accuracy of indocyanine green fluorescence imaging and multidetector row computed tomography for identifying hepatocellular carcinoma with liver explant correlation.
        Hepatol Res. 2017; 47: 1299-1307
        • DeLong J.C.
        • Murakami T.
        • Yazaki P.J.
        • et al.
        Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model.
        J Surg Res. 2017; 218: 139-143
        • Hiroshima Y.
        • Lwin T.M.
        • Murakami T.
        • et al.
        Effective fluorescence-guided surgery of liver metastasis using a fluorescent anti-CEA antibody.
        J Surg Oncol. 2015; 112: 119-124
        • Hollandsworth H.M.
        • Amirfakhri S.
        • Filemoni F.
        • et al.
        Near-infrared photoimmunotherapy is effective treatment for colorectal cancer in orthotopic nude-mouse models.
        PLoS One. 2020; 15e0234643