Preclinical evaluation of glycan-targeting monoclonal antibodies for bimodal near-infrared fluorescence and photoacoustic imaging of gastrointestinal cancers

Ruben D., Houvast, Vincent Q., Sier, Maurice, van Duijvenvoorde, Victor M., Baart, Timo, Schomann, Jia Xin, Chua, Mireille, Vankemmelbeke, Lindy G., Durrant, Daniëlle, Krijgsman, Pieter, de Heer, Gert Jan, Hassing, J. Sven D., Mieog, A. Stijn L.P., Crobach, Jacobus, Burggraaf, Peter J.K., Kuppen, Alexander L., Vahrmeijer

EJNMMI Research |

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-Lea/c/x) and CH129-800CW (anti-sdi-Lea) for bimodal NIRF/PA imaging of gastrointestinal cancers. Results: Using immunohistochemistry, we found that Lea/c/x and sdi-Lea were highly expressed in gastric and colorectal cancer tissue, with limited expression in healthy surrounding tissue, except for strong Lea/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 4.8 ± 1.4 and 4.9 ± 0.5 for the HT-29_luc2 model, and 2.5 ± 0.3 and 2.9 ± 0.4 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.