Tumor targeting of ¹²⁵I-labeled anti-EGFR monoclonal antibody LA22 in HT-29 human colon cancer

Tumor targeting of 125 I-labeled anti-EGFR monoclonal antibody LA22 in HT-29 human colon cancer 1 first-author 1 1 1 corresp Corresponding author. E-mail address: liuzf@bjmu.edu.cn Corresponding author. E-mail address: liuzf@bjmu.edu.cn liuzf@bjmu.edu.cn Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China Epidermal growth factor receptor (EGFR) plays a critical role in proliferation, apoptosis, angiogenesis, invasiveness and distant metastasis of tumors. In this study, the tumor targeting properties of anti-EGFR monoclonal antibody (mAb) LA22 in a colon cancer mouse model are evaluated. The results from flow cytometry assay and immunofluorescent staining clearly showed that HT-29 human colon cancer cells were EGFR positive, and the binding of mAb LA22 to the HT-29 cell surface was specific. The saturation binding experiment of 125 I-LA22 to HT-29 cells revealed that LA22 possessed moderate affinity to EGFR with the Kd value calculated to be 3.28±0.76 nM. The in vivo γ imaging demonstrated the specific accumulation of 125 I-LA22 in HT-29 tumor xenografts. The specific tumor targeting properties of mAb LA22 make it a good candidate for tumor targeted radioimmunotherapy of EGFR-positive tumors when it is labeled with therapeutic nuclides, such as 131 I, 177 Lu, or 90 Y. Epidermal growth factor receptor LA22 Monoclonal antibody Tumor targeting Gamma imaging References Singh A B , Harris R C . Cell Signal , 2005 , 17 : 1183 - 1193 . Cell Signal Mendelsohn J , Baselga J . Oncogene , 2000 , 19 : 6550 - 6565 . Oncogene Ciardiello F , Tortora G . Clin Cancer Res , 2001 , 7 : 2958 - 2970 . Clin Cancer Res Grandis J R , Sok J C . Pharmacol Ther , 2004 , 102 : 37 - 46 . Pharmacol Ther Ciardiello F , Damiano V , Bianco R , et al . J Natl Cancer Inst 1996 , 88 : 1770 - 1776 . J Natl Cancer Inst Speake G , Holloway B , Costello G . Curr Opin Pharmacol , 2005 , 5 : 343 - 349 . Curr Opin Pharmacol Wu D , Wang L , Chi Y , et al . Proc Natl Acad Sci USA , 1990 , 87 : 3151 - 3155 . Proc Natl Acad Sci USA Alwan H , Zoelen E , Leeuwen J . J Biol Chem , 2003 , 278 : 35781 - 35790 . J Biol Chem Shao W , Zhao S , Liu Z , et al . Biochem Biophys Res Commun , 2006 , 349 : 816 - 824 . Biochem Biophys Res Commun Liu Z , Yu Z , He W , et al . Cancer Biother Radiopharm , 2009 , 24 : 15 - 23 . Cancer Biother Radiopharm Lindmo T , Boven E , Cuttitta F , et al . J Immunol Metho , 1984 , 72 : 77 - 89 . J Immunol Metho Fujimori K , Covell D G , Fletcher J E , et al . J Nucl Med , 1990 , 31 : 1191 - 1198 . J Nucl Med 10.13538/j.1001-8042/nst.21.84-88 Supported by grants from Chinese National "863" project (2007AA02Z467) and NSF (30640067, 30870728) . 2009-07-12 2010-04-20 2021-01-19 2010 Nuclear Science and Techniques 02 21