Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice
Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice
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DOI：
10.1007/s10637-018-00718-8
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发表时间：
2019-10-01
影响因子：
3.4
通讯作者：
Chang, Chih-Hsien
中科院分区：
文献类型：
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作者：
Chang, Ya-Jen;Ho, Chung-Li;Chang, Chih-Hsien
背景西妥昔单抗是一种完全人源化的IgG1亚类单抗，可与人表皮生长因子受体(EGFR)特异性结合。虽然EGFR在正常细胞中有表达，但在许多人类肿瘤中都检测到了EGFR的过度表达，如结肠癌、直肠癌和肺癌。在本研究中，西妥昔单抗联合放疗核素Re-188对肺癌取得了较好的治疗效果。方法(188)雷西妥昔单抗静脉注射。在人NCI-H292肺癌荷瘤小鼠体内研究了其给药途径。取纳米SPECT/CT图像，评价Re-188-西妥昔单抗在小鼠体内的分布和肿瘤靶向性。以肿瘤生长抑制率、存活率为指标评价Re-188-西妥昔单抗的抗肿瘤作用。结果在纳米SPECT/CT显像中，注射Re-188-西妥昔单抗后24和48h，肿瘤内均有明显摄取。通过肿瘤生长抑制率和存活率评价Re-188-西妥昔单抗的抗肿瘤作用。Re-188-西妥昔单抗对荷瘤小鼠的平均肿瘤生长抑制率(MGI=0.049)、中位生存期和生存期(62.50d；70.07%)明显高于单次注射Re-188和西妥昔单抗。Re-188-西妥昔单抗具有协同抑制肿瘤生长的作用，其联合指数大于1(CI=6.135和9.276)。结论本研究证实了188Re-西妥昔单抗的肿瘤靶向性和定位。Re-188-西妥昔单抗的放射免疫治疗显示出协同治疗效果。这项研究的结果揭示了Re-188-西妥昔单抗在未来肿瘤学诊断和治疗应用中的潜在优势和好处。
Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear Re-188 achieved better therapeutic effect on lung cancer. Methods(188)Re-cetuximab administered by the i.v. route in human NCI-H292 lung tumor-bearing mice was investigated. NanoSPECT/CT images were taken to evaluate the distribution and tumor targeting of Re-188-cetuximab in mice. The anti-tumor effect of Re-188-cetuximab was assessed by the tumor growth inhibition, survival ratio. Results For nanoSPECT/CT imaging, a significant uptake in tumor was observed at 24 and 48 h following the injection of Re-188-cetuximab. The anti-tumor effect of Re-188-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with Re-188-cetuximab showed a better mean tumor growth inhibition rate (MGI = 0.049) and longer median survival time and lifespan (62.50 d; 70.07%) than those treated with Re-188-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for Re-188-cetuximab (CI = 6.135 and 9.276). Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of Re-188-cetuximab. The results of this study reveal the potential advantage and benefit obtained from Re-188-cetuximab for diagnosis and therapy of oncology applications in the future.