Development of Dual Receptor Enhanced Pre-Targeting Strategy—A Novel Promising Technology for Immuno-Positron Emission Tomography Imaging

Lingyi Sun, Yongkang Gai, Zhonghan Li, Xiaohui Zhang, Jianchun Li, Yongyong Ma, Huiqiang Li, Ramon F. Barajas, Dexing Zeng

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Article number2100110
JournalAdvanced Therapeutics
Issue number10
StatePublished - Oct 2021


  • dual-receptor targeting
  • epidermal growth factor receptor
  • integrin αβ
  • positron emission tomography imaging
  • pre-targeting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)


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