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PLAP Targeted Antibody-Radionuclide Conjugate for Theranostics in Pancreatic Cancer.

Yanzhao Liu1, Jingyue Gao2, Mengning Hu3

  • 1Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education, Key Laboratory for Research and Evaluation of Radiopharmaceuticals of National Medical Products Administration, Department of Nuclear Medicine, Peking University Cancer Hospital, Beijing 100142, China.

Journal of Medicinal Chemistry
|April 16, 2026
PubMed
Summary

This study developed a novel antibody-radionuclide conjugate targeting placental alkaline phosphatase (PLAP) for pancreatic cancer. The conjugate demonstrated effective PET imaging and potent radioimmunotherapy, showing promise for pancreatic cancer theranostics.

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Immunotherapy

Background:

  • Pancreatic cancer is aggressive with poor outcomes.
  • Placental alkaline phosphatase (PLAP) is overexpressed in pancreatic cancer, making it a potential theranostic target.

Purpose of the Study:

  • To develop and evaluate a novel PLAP-targeted antibody-radionuclide conjugate for pancreatic cancer theranostics.
  • To assess the conjugate's efficacy in PET imaging and radioimmunotherapy (RIT).

Main Methods:

  • Developed a humanized antibody H12F3-based conjugate for PLAP targeting.
  • Evaluated in vitro cellular uptake in PLAP-positive pancreatic cancer cells.
  • Assessed in vivo tumor targeting and retention using PET/CT imaging in mouse models.
  • Determined therapeutic efficacy through RIT in subcutaneous pancreatic cancer xenografts.

Main Results:

  • The conjugate, [89Zr]Zr-DFO-H12F3, showed high and specific uptake in PLAP-positive cells in vitro.
  • In vivo PET/CT imaging revealed significant and sustained tumor accumulation of the tracer.
  • [177Lu]Lu-DOTA-H12F3 administration led to complete suppression of tumor growth in RIT assays.

Conclusions:

  • PLAP-targeted theranostics using antibody-radionuclide conjugates are effective for pancreatic cancer.
  • The developed conjugate enables precise tumor localization via PET imaging.
  • The conjugate demonstrated potent antitumor efficacy, validating PLAP as a key theranostic target.