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.