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Therapy to target renal cell carcinoma using 131I-labeled B7-H3 monoclonal antibody

机译:使用131I标记的B7-H3单克隆抗体靶向肾细胞癌的治疗

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摘要

B7-H3 is a tumor-associated antigen that plays a critical role in potential tumor-targeted therapy. In this study, we aimed to assess the radiobiological effect of 131I-labeled B7-H3 monoclonal antibody (131I-4H7) in nude mice with human renal cell carcinoma (RCC) and evaluate the effect of 131I-4H7 on RCC treatment. The radiobiological activity and tumor uptake of 131I-4H7, and its effect on tumor growth were measured. 131I-4H7 was absorbed by the tumor and reached its maximal uptake rate (3.32% injected dose [ID]/g) at 24 h, at which point the drug concentration in the tumor was 7.36-, 2.06-, 1.80-, and 2.78-fold higher than that in muscle, kidneys, liver, and heart, respectively. Measurements and positron emission tomography–computed tomography imaging showed that tumor development was significantly inhibited by 131I-4H7. HE staining revealed that 131I-4H7 significantly injures tumor cells. Our results suggest that 131I-4H7 is markedly absorbed by the tumor and did suppress the development of RCC xenografted tumors in nude mice, which might provide a new candidate for antibody-mediated targeted radiotherapy in human RCC.
机译:B7-H3是一种与肿瘤相关的抗原,在潜在的针对肿瘤的治疗中起着至关重要的作用。在这项研究中,我们旨在评估 131 I标记的B7-H3单克隆抗体( 131 I-4H7)在患有人肾细胞癌的裸鼠中的放射生物学作用( RCC),并评估 131 I-4H7对RCC治疗的效果。测定 131 I-4H7的放射生物学活性和肿瘤吸收,及其对肿​​瘤生长的影响。 131 I-4H7被肿瘤吸收并在24小时达到最大吸收率(3.32%注射剂量[ID] / g),此时肿瘤中的药物浓度为7.36-,分别比肌肉,肾脏,肝脏和心脏高2.06倍,1.80倍和2.78倍。测量和正电子发射断层扫描-计算机断层扫描成像显示, 131 I-4H7显着抑制了肿瘤的发展。 HE染色表明, 131 I-4H7明显损伤肿瘤细胞。我们的结果表明 131 I-4H7被肿瘤明显吸收,并确实抑制了裸鼠中RCC异种移植肿瘤的发展,这可能为人RCC抗体介导的靶向放射治疗提供新的候选对象。

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