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Войти в исследования PloS one · 2014
Evaluation of (131)I-anti-angiotensin II type 1 receptor monoclonal antibody as a reporter for hepatocellular carcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hao Pan-Pan, Liu Yan-Ping, Yang Chang-Ya, Liang Ting, Zhang Chao, Song Jing, Han Jian-Kui, Hou Gui-Hua
Аннотация
BACKGROUND: 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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: (131)I-anti-AT1R mAb may be a potential target for early detection of tumor.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: (131)I-anti-AT1R mAb may be a potential target for early detection of tumor.