Prognostic value of preoperative [${}^{68}$Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics

Our aim was to assess the prognostic value of [${}^{68}$Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [${}^{68}$Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUV${}_{max}$), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUV${}_{max}$), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [${}^{68}$Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan-Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [${}^{68}$Ga]Ga-FAPI-04 PET/CT and clinicopathological factors. Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUV${}_{max}$ and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUV${}_{max}$ or TLF and pancreatic TSUV${}_{max}$ or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUV${}_{max}$ had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [${}^{68}$Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05). The in vivo [${}^{68}$Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [${}^{68}$Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival.