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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.
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.
