PLAP Targeted Antibody-Radionuclide Conjugate for Theranostics in Pancreatic Cancer

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.