Institute of Nuclear Energy Research, 1000 Wenhua Rd, Longtan District, Taoyuan City, Taiwan.
Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Invest New Drugs. 2019 Oct;37(5):961-972. doi: 10.1007/s10637-018-00718-8. Epub 2019 Jan 5.
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 achieved better therapeutic effect on lung cancer. MethodsRe-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-cetuximab in mice. The anti-tumor effect of Re-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-cetuximab. The anti-tumor effect of Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with Re-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-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for Re-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-cetuximab. The results of this study reveal the potential advantage and benefit obtained from Re-cetuximab for diagnosis and therapy of oncology applications in the future.
西妥昔单抗是一种完全人源化 IgG1 亚类单克隆抗体，特异性结合人表皮生长因子受体（EGFR）。尽管 EGFR 在正常细胞中表达，但在许多人类癌症中，如结肠、直肠和肺癌中，都检测到 EGFR 的过度表达。在这项研究中，西妥昔单抗与放射核 Re 联合应用于肺癌取得了更好的治疗效果。
研究了静脉途径给予人 NCI-H292 肺癌荷瘤小鼠的 Re-西妥昔单抗。通过 NanoSPECT/CT 图像评估 Re-西妥昔单抗在小鼠体内的分布和肿瘤靶向性。通过肿瘤生长抑制率和生存比评估 Re-西妥昔单抗的抗肿瘤作用。
对于 NanoSPECT/CT 成像，在注射 Re-西妥昔单抗后 24 和 48 小时，肿瘤中观察到明显的摄取。通过肿瘤生长抑制率和生存比评估 Re-西妥昔单抗的抗肿瘤作用。与单独注射 Re-培美曲塞和西妥昔单抗相比，接受 Re-西妥昔单抗治疗的荷瘤小鼠显示出更好的平均肿瘤生长抑制率（MGI=0.049）和更长的中位生存时间和寿命（62.50 d；70.07%）。对于 Re-西妥昔单抗，观察到协同的肿瘤生长抑制作用，组合指数超过 1（CI=6.135 和 9.276）。
本研究证实了 188Re-西妥昔单抗的肿瘤靶向性和定位。证明了 Re-西妥昔单抗放射免疫治疗的协同治疗效果。该研究的结果揭示了 Re-西妥昔单抗在未来肿瘤学诊断和治疗中的潜在优势和益处。
