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Tumor Biology

, Volume 37, Issue 7, pp 9121–9129 | Cite as

Evaluation of 188Re-labeled NGR–VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts

  • Wenhui Ma
  • Yahui Shao
  • Weidong Yang
  • Guiyu Li
  • Yingqi Zhang
  • Mingru Zhang
  • Changjing Zuo
  • Kai Chen
  • Jing Wang
Original Article

Abstract

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine–glycine–arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR–VEGI fusion protein was prepared and labeled with 188Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that 188Re-NGR–VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of 188Re-NGR–VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR–VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of 188Re-NGR–VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of 188Re-NGR–VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that 188Re-NGR–VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.

Keywords

Vascular endothelial growth inhibitor CD13 Re-188 Imaging Therapy 

Notes

Acknowledgments

We thank Professor Liwen Li, Xiaochang Xue, and Entai Hou from Northwest University and Hongdie Jiang from the Second Military Medical University for their technical assistance. This work was supported by the Key Program of National Natural Science Foundation of China (Grant No. 81230033), the Major State Basic Research Development Program (Grant No. 2011CB707704), the Major Instrument of National Natural Science Foundation Research Project (Grant No. 81227901), the Major Program of National Natural Science Foundation of China (Grant No. 81090270), the General Program of National Natural Science Foundation of China (Grant No. 81371594), the International Cooperation Program of Xijing Hospital (Grant No. XJZT13G02), and the USC Department of Radiology.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_4810_MOESM1_ESM.doc (92 kb)
Figure S1 (DOC 92 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Wenhui Ma
    • 1
    • 5
  • Yahui Shao
    • 1
    • 2
  • Weidong Yang
    • 1
  • Guiyu Li
    • 1
  • Yingqi Zhang
    • 3
  • Mingru Zhang
    • 1
  • Changjing Zuo
    • 4
  • Kai Chen
    • 5
  • Jing Wang
    • 1
  1. 1.Department of Nuclear Medicine, Xijing HospitalThe Fourth Military Medical UniversityXi’anChina
  2. 2.Department of Nuclear MedicineGeneral Hospital of Jinan Military RegionJinanChina
  3. 3.The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of PharmacyThe Fourth Military Medical UniversityXi’anChina
  4. 4.Department of Nuclear Medicine, Changhai HospitalThe Second Military Medical UniversityShanghaiChina
  5. 5.Molecular Imaging Center, Department of Radiology, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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