BackgroundFinding 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 131I-anti-AT1R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma.Methodology/Principal FindingsAT1R mAb or isotype IgG was radioiodinated with 131I and the radiochemical purity and stability of the two imaging agents and the affinity of 131I-anti-AT1R mAb against AT1R were measured. 3.7 MBq 131I-anti-AT1R mAb or isotype 131I-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 131I-anti-AT1R mAb were studied. 131I-anti-AT1R mAb and 131I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The 131I-anti-AT1R mAb group showed much clearer whole-body images for observing hepatocellular carcinoma than the 131I-IgG group. The biodistributions of the two imaging agents suggested that hepatocellular carcinoma tissue uptook more 131I-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 131I-IgG (%ID/g = 0.42±0.06 and T/NT ratio = 1.33±0.08 at 48 h). The pharmacokinetics of 131I-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.Conclusions/Significance 131I-anti-AT1R mAb may be a potential target for early detection of tumor.
Toll-like receptor 5 (TLR5) is overexpressed in several cancers and metastases, and presents an enticing target for molecular imaging of primary tumors. In the present study, 131I-anti-TLR5 monoclonal antibody (mAb) was evaluated for its use as a novel radiotracer for imaging hepatocarcinoma in mice bearing H22 tumors. The expression of TLR5 was analyzed by quantitative polymerase chain reaction and immunohistochemistry. The anti-TLR5 mAb and isotype immunoglobulin G (IgG) were radiolabeled with iodine-131 by the Iodogen method. The in vitro stability of iodinalized probes was determined in serum or saline for a series of times, and then evaluated with radio-thin-layer chromatography. The biodistribution study and autoradiography were performed in H22 tumor-bearing mice. It was found that H22-xenografted tumor tissue exhibited a higher level of TLR5 expression compared with normal liver tissues. 131I-anti-TLR5 mAb and 131I-IgG were obtained subsequent to purification, with high radiochemical purity (>95%), and remained stable for 48 h in human serum. The target-to-non-target ratio in the 131I-anti-TLR5 mAb group was significantly higher compared with the 131I-IgG group. The biodistribution study and autoradiography demonstrated that 131I-anti-TLR5 mAb was specifically retained in hepatocarcinoma with a high tumor uptake. Altogether, these results show that 131I-anti-TLR5 mAb is capable of detecting lesions in a TLR5-expressing tumor, with high target selectivity, and may offer a promising agent for hepatocarcinoma diagnosis and encourage further investigation.
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