Dynamic Expression of Fibroblast Activation Protein (FAP) During Chronic Pancreatitis (CP) Progression in Mice and...

Currently, effective methods for the early diagnosis of Chronic Pancreatitis (CP) remain limited. PANCREATIC STELLATE CELLS (PSCs) in pancreatitis are critical drivers of CP progression, and PSCs are known to overexpress Fibroblast Activation Protein (FAP) in inflamed pancreatic tissue. This study aims to investigate the correlation between the dynamic changes in FAP expression by PSCs and CP progression, and to evaluate the feasibility of three FAP inhibitor (FAPI)-based tracers for early CP diagnosis.

Caerulein-treated PRSS1 transgenic mice (PRSS1Tg) were categorized into four groups based on the development stage of CP. The pancreatic pathology was observed using HE and Masson staining. Moreover, immunohistochemistry, immunofluorescence, and qRT-PCR were employed to further analyze the pancreas. Additionally, near-infrared in vivo fluorescence imaging was performed with ICG-FAPI- 04, whereas Micro-PET/CT was performed with 68Ga-FAPI-04 and 18F-FAPI-42. The results were subsequently observed and analyzed.

Experiments revealed that FAP was overexpressed in CP, with its expression peaking at 2 weeks. In vivo near-infrared imaging using ICG-FAPI-04 failed to effectively assess pancreatic morphology and fibrosis at the 2-week time point in the CP model mice. In micro-PET/CT evaluations of CP model mice at two weeks, 18FFAPI- 42 demonstrated superior visualization of pancreatic morphology and fibrosis compared to 68Ga-FAPI-04.

The near-infrared probe ICG-FAPI-04 shows limited efficacy, but its performance could be improved by increasing hydrophilicity or adopting NIR-II imaging. In comparison, FAPI-based PET/CT-especially using 18F-FAPI-42-offers clear visualization of pancreatic morphology, positioning it as a highly promising tool for CP detection.

This study demonstrated dynamic FAP expression during CP progression. FAP-targeted tracers were shown to sensitively visualize the pancreatic morphology reflecting fibrosis severity, validating their feasibility for early CP diagnosis.