Evaluation of (131)I-Anti-Angiotensin II Type 1 Receptor Monoclonal Antibody as a Reporter for Hepatocellular Carcinoma

BACKGROUND: Finding a specific agent is useful for early detection of tumor. Angiotensin II type 1 receptor (AT(1)R) 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-AT(1)R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: AT(1)R 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-AT(1)R mAb against AT(1)R were measured. 3.7 MBq (131)I-anti-AT(1)R 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-AT(1)R mAb were studied. (131)I-anti-AT(1)R mAb and (131)I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The (131)I-anti-AT(1)R 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-AT(1)R 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-AT(1)R 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. CONCLUSIONS/SIGNIFICANCE: (131)I-anti-AT(1)R mAb may be a potential target for early detection of tumor.