Radioimunoimaging Of ～(131)I-labelled Monoclonal Antibody Against IGF1R In Nude Mice Bearing Human Hepatocellular Carcinoma

Insulin like growth factor 1 exerts its biological functions by specifically binding to its receptor (type 1 receptor of insulin like growth factor, IGF1R). IGF1R is required for growth, transformation, and protection from apoptosis in tumor cells. In recent years, studies on IGF1R were focused on expression of IGF1R and treatment of tumor cells with antisense oligonucleotides of IGF1R in vitro and in vivo.This study aims to establish a model of human hepatocelluar carcinoma (HCC) in nude mice, determine the biodistribution of 131I-labelled 1H7(monoclonal antibody against IGF1R) in this model and to explore the feasibility of radioimmunoimaging (RII) in HCC with this labelled antibody.Methods: Using cell culturing, immunohistochemistry, receptor number on cells determinating, tumor cells inoculating, iodin labelling, scintiphotography, radioactivity measuring, and other techniques, we established a HCC model in nude mice, detected the expression of IGF1R in HepG2 cells and in the xenografts, observed the effects of 1H7 on growth of HepG2 cells. Scintigraphy and tumor/non-tumor (T/NT) values were also performed at different phases after injection of this radiolabelled antibody. Results: HepG2 cells formed xenografts in all nude mice after inoculated subcutaneously. HepG2 cells and grafts strongly expressed IGF1R. The labelling rate of 131I to 1H7 was 64.6%, and this labelled antibody bound to IGF1R with an affinity contant of 1.42×1011L/mol. After purification by Sephadex G-50, the radiochemistry purity of 131I-1H7 was 96.3%.Stored at room temperature, 4℃ or -20℃ for even 3 half-lifes of 131I(24days),the radiochemistry purity of 131I-1H7 remained above 90.0%. 1H7 inhibited the growth of HepG2 cells in a dose and time dependent manner. RII of xenografts in nude mice with this radioactive antibody, the best images were gained at 96 hours post antibodyinjection. At the same time, the T/NT value in this tumor model reached its peak.Conclusions: HepG2 cells express IGF1R strongly. When inject the HepG2 cells subcutaneously into nude mice, the sites of inoculation can form xenografts easily, and the grafts express IGF1R yet. The radiochemistry purity and immune activity of 131I labelled 1H7 meets the needs of RII, and it is stable in vitro. Radioimmunoimaging with 131I-1H7 in nude mice loading HCC, a clear image and a highest T/NT value can be got at 96 hours post labelled antibody administration. Growth inhibition of HepG2 cells response to 1H7 is dose and time dependent. These results laid a foundation for further study of clinical RII and RIT of IGF1R-positive HCC.