Abstract
1371
Objectives The epidermal growth factor receptor(EGFR)has been successfully targeted for cancer therapy. As an oncoprotein in neoplastic transformation and tumorigenicity, EGFRv has been shown functions for treatment. In recently studies, the antitumor activities of mAb CH12,an anti- EGFRv antibody ,as well as cetuximab , have been demonstrated to promised therapeutic agent for treating hepatocellular carcinoma.Here,we report for the radioimmunotherapy of EGFRv-positive gliomas using βemitter 131I labeled CH12.
Methods Antibody CH12 was labeled with 131I by Iodogen.The radiochemical purity was evaluated with TLC. Stavility was tested in both room temperature and bovine serum at 1,12 and 24 hour after labeling.Immunofluorescence and FACS analysis were used to detect binding ability of CH12 and U87-EGFRv cell after labeling 131I. 131I-CH12 was measured by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on U87-EGFRv cells lines after 24,72,120 and 144h with 20uCi and 40uCi.Tumor xenograft models were established with U87-EGFRv cell line in female male BALB/c nude mice.131I-CH12 have been injected per week,totally for four weeks.Tumor volume was measured every week. Micro PET/CT image were obtained at last.Cell apoptosis was analyzed by a terminal oxynucleotidyl transferase mediated dUTP biotin nick and labeling method. Histopathologic analysis of different group the tumor tissue microvessel density.
Results The binding ability of CH12 with U87-EGFRv cell is no difference between before and after labeling 131I.The lethal effect of the high dose was significantly stronger than that of the low dose.The tumor with dose of 100uCi 131I-CH12 caused growth delay and with 200uCi led to almost stop growth.
Conclusions 131I-CH12 may be a promising radioimmunotherapeutic agent to treat gliomas.