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Investigational New Drugs

, Volume 37, Issue 5, pp 961–972 | Cite as

Biodistribution, pharmacokinetics and radioimmunotherapy of 188Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice

  • Ya-Jen Chang
  • Chung-Li Ho
  • Kai-Hung Cheng
  • Wan-I Kuo
  • Wan-Chi Lee
  • Keng-Li Lan
  • Chih-Hsien ChangEmail author
PRECLINICAL STUDIES
  • 172 Downloads

Summary

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.

Keywords

188Re Cetuximab Radioimmunotherapy 

Abbreviations

AUC

Area under the curve

CI

Combination index

Cl

Clearance

CR

Complete response

CRC

Colorectal cancer

Cmax

The maximum concentration

EGFR

Epidermal growth factor receptor

FLEX

First-line erbitux in lung cancer

IR

Inhibition rate

mAbs

Monoclonal antibodies

MAA

Maximum administered activity

MGI

Growth inhibition rate

MTD

Maximum tolerated dose

NCA

Noncompartmental analysis

NHL

Non-Hodgkin’s lymphoma

ORR

Overall response rate

RIT

Radioimmunotherapy

ROI

Region of interest

T1/2z

Elimination half-life

VOIs

Volumes of interest

Notes

Acknowledgements

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.

Grants

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).

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ya-Jen Chang
    • 1
  • Chung-Li Ho
    • 1
  • Kai-Hung Cheng
    • 1
  • Wan-I Kuo
    • 1
  • Wan-Chi Lee
    • 1
  • Keng-Li Lan
    • 2
    • 3
  • Chih-Hsien Chang
    • 1
    Email author
  1. 1.Institute of Nuclear Energy ResearchTaoyuan CityTaiwan
  2. 2.Division of Radiation Oncology, Department of OncologyTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Institute of Traditional Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan

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