BACKGROUND: Near-infrared fluorescence (NIRF) imaging assists surgeons intraoperatively to achieve radical resection of malignant tissue with one centimeter depth and can be supplemented with photoacoustic imaging to increase depth-of-view. Tumor-associated carbohydrate antigens are promising targets for tumor imaging with potential advantages over protein targeting. This study preclinically evaluates the anti-glycan tracers CH88.2-800CW (anti-Le(a/c/x)) and CH129-800CW (anti-sdi-Le(a)) for bimodal NIRF/PA imaging of gastrointestinal cancers. RESULTS: Using immunohistochemistry, we found that Le(a/c/x) and sdi-Le(a) were highly expressed in gastric and colorectal cancer tissue, with limited expression in healthy surrounding tissue, except for strong Le(a/c/x) expression in healthy colorectal epithelium. Bimodal NIRF/PA imaging using CH88.2-800CW and CH129-800CW was performed on subcutaneous and orthotopic HT-29_luc2 (colon cancer) and BxPC-3_luc2 (pancreatic cancer) tumor-bearing mice, using rituximab-800CW as a negative control tracer. At 96 h post-injection, all orthotopic tumors were delineated using the clinical Artemis NIRF imager with mean CH88.2-800CW and CH129-800CW tumor-to-background ratios of 4.8â±â1.4 and 4.9â±â0.5 for the HT-29_luc2 model, and 2.5â±â0.3 and 2.9â±â0.4 for the BxPC-3_luc2 model, respectively. Similarly specific photoacoustic signal was observed within all tumors for both CH88.2-800CW and CH129-800CW. Biodistribution analyses showed high tumor fluorescence with minimal signal in healthy organs, including the liver and kidneys. CONCLUSIONS: Bimodal NIRF/PA imaging employing CH88.2-800CW and CH129-800CW facilitates real-time, high-contrast gastrointestinal tumor visualization. Given their strong and mostly tumor-specific expression, both tracers hold promise as effective imaging agents for gastrointestinal cancers, and are compelling candidates for further clinical evaluation.
Preclinical evaluation of glycan-targeting monoclonal antibodies for bimodal near-infrared fluorescence and photoacoustic imaging of gastrointestinal cancers.
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作者:Houvast Ruben D, Sier Vincent Q, van Duijvenvoorde Maurice, Baart Victor M, Schomann Timo, Chua JiaXin, Vankemmelbeke Mireille, Durrant Lindy G, Krijgsman Daniëlle, de Heer Pieter, Hassing Gert-Jan, Mieog J Sven D, Crobach A Stijn L P, Burggraaf Jacobus, Kuppen Peter J K, Vahrmeijer Alexander L
期刊: | Ejnmmi Research | 影响因子: | 3.000 |
时间: | 2025 | 起止号: | 2025 Jun 6; 15(1):67 |
doi: | 10.1186/s13550-025-01258-y |
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