Preclinical evaluation of novel FGFR2-targeting peptide probes for PET imaging and intraoperative navigation in gastric Cancer.

Fibroblast growth factor receptor 2 (FGFR2) is extensively acknowledged as a clinically significant biomarker across various cancer types, exhibiting elevated expression levels in numerous malignancies, with particularly pronounced overexpression in gastric cancer. In the present study, we refined a radioligand, [68Ga]Ga-DOTA-PF, through modification of FGFR2-targeting peptides to facilitate positron emission tomography (PET) imaging of FGFR2 expression. This radiotracer demonstrated an affinity for FGFR2 of 98.6 ± 9.27 nM, alongside superior stability and favorable pharmacokinetic characteristics. Dynamic PET imaging revealed substantial specific accumulation of [68Ga]Ga-DOTA-PF in FGFR2-positive gastric cancer tissues, allowing for rapid and precise detection of FGFR2 expression. Additionally, we engineered a highly sensitive fluorescent probe by conjugating indocyanine green, which enabled real-time intraoperative navigation of gastric cancer via accurate delineation of tumor margins in vivo. Collectively, FGFR2-targeted PET and near-infrared fluorescence (NIRF) imaging represent a promising non-invasive approach for the precise diagnosis of gastric cancer.