Comparing the clinical value of baseline [⁶⁸ Ga]Ga-FAPI-04 PET/CT and [¹⁸F]F-FDG PET/CT in pancreatic ductal adenocarcinoma: additional prognostic value of the distal pancreatitis

Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [⁶⁸ Ga]Ga–FAPI-04 and [¹⁸F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images.

Patients with suspected localized PDAC on CE-CT were recruited for static [⁶⁸ Ga]Ga-FAPI-04 and ¹⁸[F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic ⁶⁸ Ga-FAPI-04 PET/CT. The diagnostic and staging performances of the static PET/CT results were evaluated by delineating regions of interest in the primary tumor, whole pancreas, and distal pancreas in both types of scans and then evaluating correlations between the PET/CT findings and clinicopathological characteristics. Furthermore, Kaplan–Meier and hazard ratio (log-rank) methods were used to evaluate the prognostic value of the combined dynamic [⁶⁸ Ga]Ga-FAPI-04 and static [¹⁸F]F-FDG PET/CT method.

We included 49 patients with histologically confirmed PDAC adenocarcinomas; 32 underwent 60-min dynamic [⁶⁸ Ga]Ga-FAPI-04 PET/CT imaging simultaneously. The static [⁶⁸ Ga]Ga-FAPI-04 method had significantly higher accuracy and uptake values than the static [¹⁸F]F-FDG method for primary PDAC lesions, metastatic lymph nodes, and distal metastases. Furthermore, 18.4% and 10.2% of the patients’ stages changed after using the [⁶⁸ Ga]Ga-FAPI-04 and [¹⁸F]F-FDG PET/CT methodologies, respectively, compared to the CE-CT-designated stage. The Ki values obtained from dynamic [⁶⁸ Ga]Ga-FAPI-04 PET/CT did not differ between PDAC and distal obstructive pancreatitis lesions. Pathologically enlarged tumor size, poor differentiation, and perineural invasion were associated with increased [⁶⁸ Ga]Ga-FAPI-04 uptake but not with [¹⁸F]F-FDG uptake. The preoperative prognostic performance of [⁶⁸ Ga]Ga-FAPI-04 was better than that of [¹⁸F]F-FDG. Interestingly, combined [⁶⁸ Ga]Ga-FAPI-04 and [¹⁸F]F-FDG uptake results in the whole pancreas could further stratify patients based on their postoperative prognosis.

⁶[⁶⁸ Ga]Ga-FAPI-04 PET/CT was more sensitive and accurate than [¹⁸F]F-FDG PET/CT for tumor, node, and metastasis staging of PDAC identified on CE-CT. Additionally, [⁶⁸ Ga]Ga-FAPI-04 uptake was significantly associated with pathologically aggressive tumor features. Combined [⁶⁸ Ga]Ga-FAPI-04 and [¹⁸F]F-FDG PET/CT findings improved the prognostic value, potentially providing a non-invasive guide for clinical management. Finally, increased fibroblast activity in PDAC-induced obstructive pancreatitis may be associated with poor patient survival rates.