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99mTc-labeled monomeric and dimeric NGR peptides for SPECT imaging of CD13 receptor in tumor-bearing mice

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Abstract

CD13 receptor plays a critical role in tumor angiogenesis and metastasis. We therefore aimed to develop 99mTc-labeled monomeric and dimeric NGR-containing peptides, namely, NGR1 and NGR2, for SPECT imaging of CD13 expression in HepG2 hepatoma xenografts. Both NGR-containing monomer and dimer were synthesized and labeled with 99mTc. In vivo receptor specificity was demonstrated by successful blocking of tumor uptake of 99mTc-NGR dimer in the presence of 20 mg/kg NGR2 peptide. Western blot and immunofluorescence staining confirmed the CD13 expression in HepG2 cells. The NGR dimer showed higher binding affinity and cell uptake in vitro than the NGR-containing monomer, presumably due to a multivalency effect. 99mTc-Labeled monomeric and dimeric NGR-containing peptides were subjected to SPECT imaging and biodistribution studies. SPECT scans were performed in HepG2 tumor-bearing mice at 1, 4, 12, and 24 h post-injection of ~7.4 MBq tracers. The metabolism of tracers was determined in major organs at different time points after injection which demonstrated rapid, significant tumor uptake and slow tumor washout for both traces. Predominant clearance from renal and hepatic system was also observed in 99mTc-NGR1 and 99mTc-NGR2. In conclusion, monomeric and dimeric NGR peptide were developed and labeled with 99mTc successfully, while the high integrin avidity and long retention in tumor make 99mTc-NGR dimer a promising agent for tumor angiogenesis imaging.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 30970847, 30800275, 30970846), the Program of the National Basic Research and Development Program of China (Grant No. 2011CB707704), and the Major Program of National Natural Science Foundation of China (Grant No. 81090274).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China

    Wenhui Ma, Fei Kang, Zhe Wang, Weidong Yang, Guiyu Li, Xiaowei Ma & Guoquan Li

  2. State Key Laboratory of Cancer Biology, Department of Pharmacy, Biotechnology Center, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China

    Yingqi Zhang

  3. Department of Radiology, Molecular Imaging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Kai Chen

  4. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, 127# West Changle Road, Xi’an, Shaanxi, 710032, China

    Jing Wang

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  1. Wenhui Ma
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  2. Fei Kang
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  3. Zhe Wang
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  4. Weidong Yang
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  5. Guiyu Li
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  6. Xiaowei Ma
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  7. Guoquan Li
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  8. Kai Chen
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  9. Yingqi Zhang
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  10. Jing Wang
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Corresponding author

Correspondence to Jing Wang.

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Wenhui Ma and Fei Kang contributed equally to this work.

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Ma, W., Kang, F., Wang, Z. et al. 99mTc-labeled monomeric and dimeric NGR peptides for SPECT imaging of CD13 receptor in tumor-bearing mice. Amino Acids 44, 1337–1345 (2013). https://doi.org/10.1007/s00726-013-1469-1

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  • DOI: https://doi.org/10.1007/s00726-013-1469-1

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