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Gallium-68-Labeled Anti-HER2 Single-Chain Fv Fragment: Development and In Vivo Monitoring of HER2 Expression

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Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

We aimed to develop a gallium-68 (Ga-68)-labeled single-chain variable fragment (scFv) targeting the human epidermal growth factor receptor 2 (HER2) to rapidly and noninvasively evaluate the status of HER2 expression.

Procedures

Anti-HER2 scFv was labeled with Ga-68 by using deferoxamine (Df) as a bifunctional chelate. Biodistribution of [68Ga]Df-anti-HER2 scFv was examined with tumor-bearing mice and positron emission tomography (PET) imaging was performed. The changes in HER2 expression after anti-HER2 therapy were monitored by PET imaging.

Results

[68Ga]Df-anti-HER2 scFv was obtained with high radiochemical yield after only a 5-min reaction at room temperature. The probe showed high accumulation in HER2-positive xenografts and the intratumoral distribution of radioactivity coincided with HER2-positive regions. Furthermore, [68Ga]Df-anti-HER2 scFv helped visualize HER2-positive xenografts and monitor the changes in HER2 expression after anti-HER2 therapy.

Conclusion

[68Ga]Df-anti-HER2 scFv could be a promising probe to evaluate HER2 status by in vivo PET imaging, unless trastuzumab is prescribed as part of the therapy.

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Acknowledgments

The authors would like to thank FUJIFILM RI Pharma Co., Ltd. for providing gallium-67 chloride and supporting the use of 68Ge/68Ga generator. The authors would like to thank Canon Inc. for providing anti-HER2 scFv. The authors are grateful to Central Research Laboratory, Okayama University Medical School for MALDI-TOF-MS analyses, and Okayama Medical Inovation Center for the assistance of image analyses. This work was supported in part by the Research and Development Project on Molecular Probes for Detection of Biological Features on Cancer of the New Energy and Industrial Technology Development Organization (NEDO), Japan, and a Grant-in-Aid for Scientific Research (KAKENHI No. 23000005) from the Japan Society for the Promotion of Science.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Author notes

  1. Masashi Ueda

    Present address: Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, 700-8530, Japan

Authors and Affiliations

  1. Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Masashi Ueda

  2. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Masashi Ueda, Hayato Hisada, Takashi Temma, Yoichi Shimizu, Hiroyuki Kimura, Masahiro Ono & Hideo Saji

  3. Central Institute of Isotope Science, Hokkaido University, Sapporo, 060-0815, Japan

    Yoichi Shimizu

  4. Radioisotope Research Center of Kyoto University, Kyoto, 606-8501, Japan

    Hiroyuki Kimura

  5. Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Yuji Nakamoto & Kaori Togashi

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  1. Masashi Ueda
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Correspondence to Hideo Saji.

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Ueda, M., Hisada, H., Temma, T. et al. Gallium-68-Labeled Anti-HER2 Single-Chain Fv Fragment: Development and In Vivo Monitoring of HER2 Expression. Mol Imaging Biol 17, 102–110 (2015). https://doi.org/10.1007/s11307-014-0769-5

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  • DOI: https://doi.org/10.1007/s11307-014-0769-5

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