PLAP Targeted Antibody-Radionuclide Conjugate for Theranostics in Pancreatic Cancer

  • J Med Chem. 2026 May 14;69(9):11410-11420. doi: 10.1021/acs.jmedchem.6c00603.
Yanzhao Liu  1 ,  Jingyue Gao  2 ,  Mengning Hu  3 ,  Junyi Chen  4 ,  Tianyi Cen  5 ,  Mengxin Xu  5 ,  Zhibo Liu  1  3  4  5  6
Affiliations
  • 1. Key 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.
  • 2. Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 3. Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, 610213, China.
  • 4. Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • 5. Changping Laboratory, Beijing 102206, China.
  • 6. Peking University-Tsinghua University Center for Life Sciences, Beijing 100871, China.
PMID: 41989751 DOI: 10.1021/acs.jmedchem.6c00603
Abstract

Pancreatic Cancer remains highly aggressive with a poor prognosis. The cell-surface oncofetal antigen placental Alkaline Phosphatase (PLAP) is overexpressed in pancreatic Cancer, rendering it a promising theranostic target. Herein, we develop a novel PLAP-targeted antibody-radionuclide conjugate based on the humanized antibody H12F3 and evaluate its performance for both positron emission tomography (PET) imaging and radioimmunotherapy (RIT) in pancreatic Cancer models. In vitro, [89Zr]Zr-DFO-H12F3 showed specific and high uptake in PLAP-positive HPAC cells (65.9 ± 0.9% at 8 h). In vivo PET/CT imaging in HPAC xenografts revealed high and sustained tumor uptake of [89Zr]Zr-DFO-H12F3, with a peak SUVmean of 4.9 ± 0.4 at 120 h. In RIT assays, administration of 3.7 MBq [177Lu]Lu-DOTA-H12F3 resulted in complete suppression of subcutaneous HPAC xenograft growth. This study establishes PLAP-targeted theranostics, enabling precise tumor localization and potent antitumor efficacy, validating PLAP as a highly effective theranostic target for pancreatic Cancer.

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