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Báo cáo toán học: " Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets"

Tuyển tập các báo cáo nghiên cứu khoa học ngành toán học được đăng trên tạp chí toán học quốc tế đề tài: Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets | Cohen et al. EJNMMI Research 2011 1 31 http www.ejnmmires.eom content 1 1 31 9 EJNMMI Research a SpringerOpen Journal ORIGINAL RESEARCH Open Access Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets 111 12 Ruth Cohen Marieke A Stammes Inge HC de Roos Marijke Stigter-van Walsum Gerard WM Visser and Guus AMS van Dongen1 Abstract Background Photoimmunodetection in which monoclonal antibodies mAbs are labeled with fluorescent dyes might have clinical potential for early detection and characterization of cancer. For this purpose the dye should be coupled in an inert way to mAb. In this study different equivalents of IRDye800CW a near-infrared fluorescent dye were coupled to 89Zr-labeled cetuximab and bevacizumab and conjugates were evaluated in biodistribution studies. Radiolabeled mAbs were used to allow accurate quantification for assessment of the number of dye groups that can be coupled to mAbs without affecting their biological properties. Methods 89Zr-cetuximab and 89Zr-bevacizumab containing 0.5 89Zr-desferal group per mAb molecule were incubated with 1 to 10 eq IRDye800CW at pH 8.5 for 2 h at 35 C and 89Zr-mAb-IRDye800CW conjugates were purified by a PD10 column using 0.9 NaCl as eluent. HPLC analysis at 780 nm was used to assess conjugation efficiency. In vitro stability measurements were performed in storage buffer 0.9 NaCl or PBS at 4 C and 37 C and human serum at 37 C. 89Zr-mAb-IRDye800CW conjugates and 89Zr-mAb conjugates as reference were administered to nude mice bearing A431 cetuximab or FaDu bevacizumab xenografts and biodistribution was assessed at 24 to 72 h after injection. Results Conjugation efficiency of IRDye800CW to 89Zr-mAbs was approximately 50 on an average 0.5 to 5 eq IRDye800CW was conjugated. All conjugates showed optimal immunoreactivity and were 95 stable in storage buffer at 4 C and 37 C and human serum at 37 C for at least 96 h. In biodistribution studies with 89Zr-cetuximab-IRDye800CW .