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 188Re achieved better therapeutic effect on lung cancer. Methods188Re-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 188Re-cetuximab in mice. The anti-tumor effect of 188Re-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 188Re-cetuximab. The anti-tumor effect of 188Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with 188Re-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 188Re-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for 188Re-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 188Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from 188Re-cetuximab for diagnosis and therapy of oncology applications in the future.
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Area under the curve
- Cmax :
The maximum concentration
Epidermal growth factor receptor
First-line erbitux in lung cancer
Maximum administered activity
Growth inhibition rate
Maximum tolerated dose
Overall response rate
Region of interest
- T1/2z :
Volumes of interest
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The authors would like to thank C. C. Liang, W. L. Lo, Y. R. Huang and M. W. Chen for help with the biodistribution study of 188Re-cetuximab.
This study was supported by the grants from Ministry of Economic Affairs of Taiwan (Grant Number 107-EC-17-A-22-1309) and Taipei Veterans General Hospital (Grant Number V106D29–003-MY3–2).
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Chang, Y., Ho, C., Cheng, K. et al. Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice. Invest New Drugs 37, 961–972 (2019). https://doi.org/10.1007/s10637-018-00718-8