TY - JOUR
T1 - Development of Dual Receptor Enhanced Pre-Targeting Strategy—A Novel Promising Technology for Immuno-Positron Emission Tomography Imaging
AU - Sun, Lingyi
AU - Gai, Yongkang
AU - Li, Zhonghan
AU - Zhang, Xiaohui
AU - Li, Jianchun
AU - Ma, Yongyong
AU - Li, Huiqiang
AU - Barajas, Ramon F.
AU - Zeng, Dexing
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/10
Y1 - 2021/10
N2 - Positron emission tomography (PET) imaging has become an important diagnostic tool. Various pre-targeting systems have been reported to address limitations associated with traditional immuno-PET. However, the application of these mono-receptor based pre-targeting (MRPT) strategies is limited to non-internalizable antibodies, and the tumor uptake is usually much lower than that in the corresponding immuno-PET. To circumvent these limitations, the first dual-receptor enhanced pre-targeting (DRPT) system is developed through entrapping the tumor-receptor-specific radioligand by the pre-administered antibody. Besides the similar ligation pathway happens in MRPT, incorporation of a tumor-receptor-specific peptide into the radioligand in DRPT enhances both concentration and retention of the radioligand on tumor, promoting its ligation with pre-administered antibody on cell-surface and/or internalized into tumor-cells. In this study, 64Cu-based DRPT shows superior performance over corresponding MRPT and immuno-PET using internalizable antibodies. Besides, the compatibility of DRPT with short-lived and generator-produced 68Ga is demonstrated, leveraging its advantage in reducing radio-dose exposure. Furthermore, the feasibility of reducing the amount of the pre-administered antibody is confirmed, indicating the cost saving potential of DRPT. In summary, synergizing advantages of dual-receptor targeting and pre-targeting, it is expect that this DRPT strategy can become a breakthrough technology in the field of antibody-based molecular imaging.
AB - Positron emission tomography (PET) imaging has become an important diagnostic tool. Various pre-targeting systems have been reported to address limitations associated with traditional immuno-PET. However, the application of these mono-receptor based pre-targeting (MRPT) strategies is limited to non-internalizable antibodies, and the tumor uptake is usually much lower than that in the corresponding immuno-PET. To circumvent these limitations, the first dual-receptor enhanced pre-targeting (DRPT) system is developed through entrapping the tumor-receptor-specific radioligand by the pre-administered antibody. Besides the similar ligation pathway happens in MRPT, incorporation of a tumor-receptor-specific peptide into the radioligand in DRPT enhances both concentration and retention of the radioligand on tumor, promoting its ligation with pre-administered antibody on cell-surface and/or internalized into tumor-cells. In this study, 64Cu-based DRPT shows superior performance over corresponding MRPT and immuno-PET using internalizable antibodies. Besides, the compatibility of DRPT with short-lived and generator-produced 68Ga is demonstrated, leveraging its advantage in reducing radio-dose exposure. Furthermore, the feasibility of reducing the amount of the pre-administered antibody is confirmed, indicating the cost saving potential of DRPT. In summary, synergizing advantages of dual-receptor targeting and pre-targeting, it is expect that this DRPT strategy can become a breakthrough technology in the field of antibody-based molecular imaging.
KW - dual-receptor targeting
KW - epidermal growth factor receptor
KW - integrin αβ
KW - positron emission tomography imaging
KW - pre-targeting
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U2 - 10.1002/adtp.202100110
DO - 10.1002/adtp.202100110
M3 - Article
AN - SCOPUS:85113156603
SN - 2366-3987
VL - 4
JO - Advanced Therapeutics
JF - Advanced Therapeutics
IS - 10
M1 - 2100110
ER -