Jeong Kyoungyun, Koo Annie Eunhee, Yoo Jaeun, Shin Ji-Yeon, Lim Leena, Kim Hyun Myong, Park Ji-Yong, Lee Yun-Sang, Kwak Yoon-Jin, Lee Hye Seung, Yoo Yie-Ri, Framery Bérénice, Dumas Karen, Cailler Françoise, Pèlegrin André, Park Do-Joong, Yang Han-Kwang, Kong Seong-Ho, Lee Hyuk-Joon
Cancer Research Institute, College of Medicine, Seoul National University, 101 Daehak-ro, Jongro-gu, Seoul 03080, Republic of Korea.
Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongro-gu, Seoul 03080, Republic of Korea.
Cancers (Basel). 2025 Sep 8;17(17):2937. doi: 10.3390/cancers17172937.
Near-infrared fluorescence-guided surgery (FGS) using cancer-specific tracers is promising for tailored gastric cancer (GC) surgery. Carcinoembryonic antigen (CEA) is a potential target due to its high expression in various digestive cancers, including GC. SGM-101, a chimeric anti-CEA monoclonal antibody conjugated with the near-infrared dye BM-104, was evaluated in GC. CEA expression was identified in GC cell lines at the mRNA and protein levels. Xenograft models (MKN-45, SNU-16, SNU-668, 85As2mLuc) were established in mice and injected with SGM-101 or PBS. Biodistribution was monitored using in vivo fluorescence imaging. Tumors were further analyzed by immunofluorescence. In a peritoneal carcinomatosis model, 85As2mLuc cells were injected intraperitoneally, and tumors were evaluated by bioluminescence and fluorescence and histology. MKN-45, SNU-16, and 85As2mLuc were CEA-positive, while SNU-668 was CEA-negative. Flow cytometry confirmed CEA expression: MKN-45 (98%), SNU-16 (85.6%), SNU-668 (6.42%) and 85As2mLuc (78.4%). SGM-101 selectively targeted CEA-expressing tumors, with fluorescence peaking at 48 h, and immunofluorescence verified localization in tumor cells. In the peritoneal models, SGM-101 enabled precise detection of CEA-positive tumors. This study provides the first evidence for the feasibility of SGM-101 in gastric cancer, demonstrating its novelty and translational potential as a cancer-specific imaging agent for fluorescence-guided surgery.
使用癌症特异性示踪剂的近红外荧光引导手术（FGS）在胃癌（GC）的精准手术中具有广阔前景。癌胚抗原（CEA）因其在包括胃癌在内的多种消化系统癌症中高表达，是一个潜在靶点。SGM-101是一种与近红外染料BM-104偶联的嵌合抗CEA单克隆抗体，已在胃癌中进行了评估。在胃癌细胞系中从mRNA和蛋白质水平鉴定了CEA表达。在小鼠中建立了异种移植模型（MKN-45、SNU-16、SNU-668、85As2mLuc），并注射SGM-101或磷酸盐缓冲盐水（PBS）。使用体内荧光成像监测生物分布。通过免疫荧光对肿瘤进行进一步分析。在腹膜癌模型中，腹腔内注射85As2mLuc细胞，并通过生物发光、荧光和组织学对肿瘤进行评估。MKN-45、SNU-16和85As2mLuc为CEA阳性，而SNU-668为CEA阴性。流式细胞术证实了CEA表达：MKN-45（98%）、SNU-16（85.6%）、SNU-668（6.42%）和85As2mLuc（78.4%）。SGM-101选择性地靶向表达CEA的肿瘤，荧光在48小时达到峰值，免疫荧光证实其在肿瘤细胞中的定位。在腹膜模型中，SGM-101能够精确检测CEA阳性肿瘤。本研究为SGM-101在胃癌中的可行性提供了首个证据，证明了其作为荧光引导手术的癌症特异性成像剂的新颖性和转化潜力。
