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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Small Molecule Therapeutics

Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD

Liang Zhao, Haojun Chen, Zhide Guo, Kaili Fu, Lanling Yao, Li Fu, Weixi Guo, Xuejun Wen, Orit Jacobson, Xianzhong Zhang, Long Sun, Hua Wu, Qin Lin and Xiaoyuan Chen
Liang Zhao
1Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Haojun Chen
2Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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  • For correspondence: leochen0821@foxmail.com linqin05@163.com shawn.chen@nih.gov
Zhide Guo
3State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
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Kaili Fu
1Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Lanling Yao
2Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Li Fu
4Department of Pathology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Weixi Guo
5Department of Thoracic Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Xuejun Wen
3State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
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Orit Jacobson
6Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland.
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Xianzhong Zhang
3State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
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Long Sun
2Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Hua Wu
2Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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Qin Lin
1Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
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  • For correspondence: leochen0821@foxmail.com linqin05@163.com shawn.chen@nih.gov
Xiaoyuan Chen
6Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland.
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  • For correspondence: leochen0821@foxmail.com linqin05@163.com shawn.chen@nih.gov
DOI: 10.1158/1535-7163.MCT-19-1098 Published October 2020
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Abstract

Currently, most patients with non–small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor five-year survival rate. Therefore, intensive research aimed at finding novel therapeutic strategies has been ongoing; experimental models that reliably emulate NSCLC disease are greatly needed to predict responses to novel therapeutics. Therefore, we developed patient-derived xenograft (PDX) models of NSCLC, which we then used to evaluate the therapeutic efficacy of 177Lu-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin αvβ3. In this study, three different groups of NSCLC-PDXs were successfully established, all of which maintained the same IHC and genetic characteristics of the human primary tumor. The two NSCLC-PDX groups with intense and low expression of integrin αvβ3 (denoted as PDXαvβ3+ and PDXαvβ3-) were chosen as the experimental models to evaluate the in vivo biological behavior of 177Lu-EB-RGD. In SPECT imaging and biodistribution studies, 177Lu-EB-RGD showed significantly higher accumulation in PDXαvβ3+ and PDXαvβ3- models than its corresponding monomer 177Lu-RGD. A single dose of 18.5 MBq 177Lu-EB-RGD was enough to completely eradicate the tumors in PDXαvβ3+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDXαvβ3-: a single dose of 29.6 MBq 177Lu-EB-RGD led to a significant delay in tumor growth as compared with that in the control or 177Lu-RGD group. The preclinical data from the use of this model suggest that 177Lu-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Mol Cancer Ther 2020;19:2034–43

  • Received November 23, 2019.
  • Revision received May 1, 2020.
  • Accepted August 7, 2020.
  • Published first August 26, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 19 (10)
October 2020
Volume 19, Issue 10
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Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD
Liang Zhao, Haojun Chen, Zhide Guo, Kaili Fu, Lanling Yao, Li Fu, Weixi Guo, Xuejun Wen, Orit Jacobson, Xianzhong Zhang, Long Sun, Hua Wu, Qin Lin and Xiaoyuan Chen
Mol Cancer Ther October 1 2020 (19) (10) 2034-2043; DOI: 10.1158/1535-7163.MCT-19-1098

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Targeted Radionuclide Therapy in Patient-Derived Xenografts Using 177Lu-EB-RGD
Liang Zhao, Haojun Chen, Zhide Guo, Kaili Fu, Lanling Yao, Li Fu, Weixi Guo, Xuejun Wen, Orit Jacobson, Xianzhong Zhang, Long Sun, Hua Wu, Qin Lin and Xiaoyuan Chen
Mol Cancer Ther October 1 2020 (19) (10) 2034-2043; DOI: 10.1158/1535-7163.MCT-19-1098
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