Tumor Targeting and Imaging Using Cyclic RGD-PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine-125

Authors

  • Young-Hwa Kim,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-744, South Korea
    3. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea
    Current affiliation:
    1. Y.H.K, J.J., and S.H.H. contributed equally to this work.
    Search for more papers by this author
  • Jongho Jeon,

    1. Department of Chemistry, Seoul National University, Seoul 151-747, South Korea
    Current affiliation:
    1. Y.H.K, J.J., and S.H.H. contributed equally to this work.
    Search for more papers by this author
  • Su Hyun Hong,

    1. Department of Chemistry, Seoul National University, Seoul 151-747, South Korea
    Current affiliation:
    1. Y.H.K, J.J., and S.H.H. contributed equally to this work.
    Search for more papers by this author
  • Won-Kyu Rhim,

    1. Department of Chemistry, Seoul National University, Seoul 151-747, South Korea
    Search for more papers by this author
  • Yun-Sang Lee,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    Search for more papers by this author
  • Hyewon Youn,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea
    3. Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul 110-744, South Korea
    Search for more papers by this author
  • June-Key Chung,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-744, South Korea
    3. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea
    Search for more papers by this author
  • Myung Chul Lee,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul 110-744, South Korea
    Search for more papers by this author
  • Dong Soo Lee,

    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Molecular Medicine and Biopharmaceutical Sciences, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul 110-744, South Korea
    Search for more papers by this author
  • Keon Wook Kang,

    Corresponding author
    1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    2. Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea
    • Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea
    Search for more papers by this author
  • Jwa-Min Nam

    Corresponding author
    1. Department of Chemistry, Seoul National University, Seoul 151-747, South Korea
    • Department of Chemistry, Seoul National University, Seoul 151-747, South Korea.
    Search for more papers by this author

Abstract

Radioactive iodine-labeled, cyclic RGD-PEGylated gold nanoparticle (AuNP) probes are designed and synthesized for targeting cancer cells and imaging tumor sites. These iodine-125-labeled cRGD–PEG–AuNP probes are stable in various conditions including a range of pHs and high salt and temperature conditions. These probes can target selectively and be taken up by tumor cells via integrin αvβ3-receptor-mediated endocytosis with no cytotoxicity. The probes show a significant increase in the avidity of αvβ3 integrin compared to the corresponding free cRGD peptides. In-vivo SPECT/CT imaging results show that the iodine-125-labeled cRGD–PEG–AuNP probes can target the tumor site as soon as 10 min after injection, and also that cyclic RGD peptides are needed for efficient and long-term in-vivo monitoring. The results suggest that the probes circulate through the whole body, including renal filtration, and are excretable. These promising results show that radioactive-iodine-labeled gold nanoprobes have potential for highly specific and sensitive tumor imaging or for use as angiogenesis-targeted SPECT/CT imaging probes.

Ancillary