Evaluation of (131)I-anti-angiotensin II type 1 receptor monoclonal antibody as a reporter for hepatocellular carcinoma.

Abstract

Finding a specific agent is useful for early detection of tumor. Angiotensin II type 1 receptor (AT1R) was reported to be elevated in a variety of tumors and participate in tumor progression. The aim of our study was to evaluate whether (131)I-anti-AT1R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma. AT1R mAb or isotype IgG was radioiodinated with (131)I and the radiochemical purity and stability of the two imaging agents and the affinity of (131)I-anti-AT1R mAb against AT1R were measured. 3.7 MBq (131)I-anti-AT1R mAb or isotype (131)I-IgG was intravenously injected to mice with hepatocellular carcinoma through tail vein, and then the whole-body autoradiography and biodistribution of the two imaging agents and the pharmacokinetics of (131)I-anti-AT1R mAb were studied. (131)I-anti-AT1R mAb and (131)I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The (131)I-anti-AT1R mAb group showed much clearer whole-body images for observing hepatocellular carcinoma than the (131)I-IgG group. The biodistributions of the two imaging agents suggested that hepatocellular carcinoma tissue uptook more (131)I-anti-AT1R mAb than other tissues (%ID/g = 1.82±0.40 and T/NT ratio = 7.67±0.64 at 48 h), whereas hepatocellular carcinoma tissue did not selectively uptake (131)I-IgG (%ID/g = 0.42±0.06 and T/NT ratio = 1.33±0.08 at 48 h). The pharmacokinetics of (131)I-anti-AT1R mAb was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. These results were further verified by real-time RT-PCR, immunohistochemistry staining and Western blot. (131)I-anti-AT1R mAb may be a potential target for early detection of tumor.