TY - JOUR
T1 - Gallium-68-Labeled Anti-HER2 Single-Chain Fv Fragment
T2 - Development and In Vivo Monitoring of HER2 Expression
AU - Ueda, Masashi
AU - Hisada, Hayato
AU - Temma, Takashi
AU - Shimizu, Yoichi
AU - Kimura, Hiroyuki
AU - Ono, Masahiro
AU - Nakamoto, Yuji
AU - Togashi, Kaori
AU - Saji, Hideo
N1 - Funding Information:
The authors would like to thank FUJIFILM RI Pharma Co., Ltd. for providing gallium-67 chloride and supporting the use of Ge/Ga 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. 68 68
Publisher Copyright:
© 2014, Academy of Molecular Imaging and Society for Molecular Imaging.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - 17-DMAG
KW - Gallium-68
KW - Human epidermal growth factor receptor 2(HER2)
KW - Positron emission tomography (PET)
KW - Single-chain Fv Fragment (scFv)
KW - Therapy
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U2 - 10.1007/s11307-014-0769-5
DO - 10.1007/s11307-014-0769-5
M3 - Article
C2 - 25049073
AN - SCOPUS:84938591134
SN - 1536-1632
VL - 17
SP - 102
EP - 110
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 1
ER -
