评价（131）I-抗血管紧张素 II 型 1 受体单克隆抗体作为肝细胞癌报告物的价值。
Evaluation of (131)I-anti-angiotensin II type 1 receptor monoclonal antibody as a reporter for hepatocellular carcinoma.
机构信息
Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, China ; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, China.
出版信息
PLoS One. 2014 Jan 8;9(1):e85002. doi: 10.1371/journal.pone.0085002. eCollection 2014.
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.
背景
寻找特定的标志物对于肿瘤的早期发现是有用的。血管紧张素 II 型 1 型受体 (AT1R) 在多种肿瘤中被报道升高，并参与肿瘤的进展。我们的研究目的是评估 131I-抗 AT1R 单克隆抗体 (mAb) 是否是检测肝细胞癌的有效成像报告物。
方法/主要发现：用 131I 对 AT1R mAb 或同型 IgG 进行放射性碘标记，并测量两种成像剂的放射化学纯度和稳定性，以及 131I-抗 AT1R mAb 对 AT1R 的亲和力。通过尾静脉向患有肝细胞癌的小鼠静脉注射 3.7 MBq 131I-抗 AT1R mAb 或同型 131I-IgG，然后研究两种成像剂的全身放射自显影和生物分布，以及 131I-抗 AT1R mAb 的药代动力学。131I-抗 AT1R mAb 和 131I-IgG 成功进行了放射性碘标记，并且在血清中的稳定性均优于在盐水中。与 131I-IgG 组相比，131I-抗 AT1R mAb 组对肝细胞癌的全身成像更清晰。两种成像剂的生物分布表明，肝癌组织摄取了更多的 131I-抗 AT1R mAb（48 小时时 %ID/g=1.82±0.40，T/NT 比值=7.67±0.64），而肝癌组织并没有选择性地摄取 131I-IgG（48 小时时 %ID/g=0.42±0.06，T/NT 比值=1.33±0.08）。131I-抗 AT1R mAb 的药代动力学符合双室模型，具有快速分布相和缓慢下降相。这些结果进一步通过实时 RT-PCR、免疫组织化学染色和 Western blot 得到验证。
结论/意义：131I-抗 AT1R mAb 可能是肿瘤早期检测的潜在靶标。
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