Aug 14 – 18, 2023
Europe/Berlin timezone

Feasibility of the Anti-carcinoembryonic antigen Monoclonal Antibody-dye conjugate, SGM-101, for Near-infrared Fluorescent Cancer-specific Intraoperative Imaging for Gastric Cancer using Xenograft Animal Models

Aug 17, 2023, 2:18 PM
18m
Taurus 1

Taurus 1

Speaker

Ms Annie Eunhee Koo (Technical University of Munich, Seoul National University)

Description

Near-infrared fluorescence-guided surgery using cancer-specific tracers is a promising approach to balance the radicality and quality of life after surgery. Carcinoembryonic antigen (CEA) is a potential target due to its high expression in various digestive cancers, including gastric cancer (GC). This study aims to assess the feasibility of the anti-CEA chimeric monoclonal antibody-dye conjugate emitting at 705 nm, for cancer-specific intraoperative imaging using xenograft mouse models with human cancer cell lines. Four representative human gastric cancer cell lines with CEA expression differences were selected. Selective binding of SGM-101 to CEA on the surface of cancer cells was found using fluorescence-activated cell sorting analysis and immunocytochemistry. in vivo imaging system was used for imaging after intravenous administration of SGM-101 to the subcutaneous implanted models. According to the distribution of this, the highest fluorescence signal was observed 48 hours after injection in a CEA density-dependent manner. Extracted tissue at peak detection time showed a micro-distribution of SGM-101 corresponding to CEA expression evaluated by Immunohistochemistry (IHC). A peritoneal seeding model was created by injecting 85As2mLuc gastric cancer cell line, which expresses both CEA and luciferase activity, into the peritoneal cavity of BALB/c-nu mice. Fluorescence imaging conducted 48 hours after intravenous (IV) administration of SGM-101 could sensitively distinguish nodules suspected of seeding, as confirmed by luminescence imaging and pathologic evaluation. This study confirms the potential of SGM-101 as a patient-tailored surgery tool such as fluorescence-guided navigation, which can identify the metastatic pattern of gastric cancer cells during surgical operation.

References

  1. Jeong K, Kong SH, Bae SW, Park CR, Berlth F, Shin JH, Lee YS, Youn H, Koo E, Suh YS, Park DJ, Lee HJ, Yang HK. Evaluation of Near-infrared Fluorescence-conjugated Peptides for Visualization of Human Epidermal Receptor 2-overexpressed Gastric Cancer. J Gastric Cancer. 2021;21(2):191-202.
  2. Gutowski M, Framery B, Boonstra MC, Garambois V, Quenet F, Dumas K, Scherninski F, Cailler F, Vahrmeijer AL, Pèlegrin A. SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery. Surg Oncol. 2017;26(2):153-62.
  3. Boogerd LS, Hoogstins CE, Schaap DP, Kusters M, Handgraaf HJ, van der Valk MJ, Hilling DE, Holman FA, Peeters KC, Mieog JSD. Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study. The Lancet Gastroenterology & Hepatology. 2018;3(3):181-91.
Keywords Fluorescence labeled Chimeric Monoclonal Antibody; Stomach Neoplasm; Carcinoembryonic Antigen; Cancer-specific Imaging; Fluorescence-guided Surgery

Primary author

Ms Annie Eunhee Koo (Technical University of Munich, Seoul National University)

Co-authors

Prof. André Pèlegrin (IRCM, Université de Montpellier, Inserm, ICM, Montpellier, France) Dr Françoise Cailler (SurgiMAb, Montpellier, France) Prof. Han-Kwang Yang (Seoul National University) Prof. Seong-Ho Kong (Seoul National University) Prof. Hyuk-Joon Lee (Seoul National University) Prof. Do-Joong Park (Seoul National University)

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