Impact of 68Ga-FAPI PET/CT Imaging on the Therapeutic Management of Primary and Recurrent Pancreatic Ductal Adenocarcinomas

Abstract

Pancreatic ductal carcinoma (PDAC) is a highly lethal cancer, and early detection and accurate staging are critical to prolonging survival. PDAC typically has a prominent stroma including cancer-associated fibroblasts that express fibroblast activation protein (FAP). FAP is a new target molecule for PET imaging of various tumors. In this retrospective study, we describe the clinical impact of PET/CT imaging using 68Ga-labeled FAP-inhibitors (68Ga-FAPI PET/CT) in 19 patients with PDAC (7 primary, 12 progressive/recurrent). Methods: All patients underwent contrast-enhanced CT (ceCT) for TNM staging before 68Ga-FAPI PET/CT imaging. PET scans were acquired 60 min after administration of 150-250 MBq of 68Ga-labeled FAP-specific tracers. To characterize 68Ga-FAPI uptake over time, additional scans after 10 or 180 min were acquired in 6 patients. SUVmax and SUVmean values of PDAC manifestations and healthy organs were analyzed. The tumor burden according to 68Ga-FAPI PET/CT was compared with TNM staging based on ceCT and changes in oncologic management were recorded. Results: Compared with ceCT, 68Ga-FAPI PET/CT results led to changes in TNM staging in 10 of 19 patients. Eight of 12 patients with recurrent/progressive disease were upstaged, 1 was downstaged, and 3 had no change. In newly diagnosed PDAC, 1 of 7 patients was upstaged, and the staging of 6 patients did not change. Changes in oncologic management occurred in 7 patients. Markedly elevated uptake of 68Ga-FAPI in PDAC manifestations after 1 h was seen in most cases. Differentiation from pancreatitis based on static imaging 1 h after injection was challenging. With respect to imaging after multiple time points, PDAC and pancreatitis showed a trend for differential uptake kinetics. Conclusion:68Ga-FAPI PET/CT led to restaging in half of the patients with PDAC and most patients with recurrent disease compared with standard of care imaging. The clinical value of 68Ga-FAPI PET/CT should be further investigated.

Keywords: FAP; PDAC; PET; TNM; fibroblast activation protein; pancreatic ductal adenocarcinoma; staging.

© 2021 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

Graphical abstract

FIGURE 1.

Biodistribution analysis (SUVmax and SUVmean) of 19 patients with PDAC based on PET/CT imaging 1 h after injection of 68Ga-labeled FAPI tracer molecules (FAPI-4 in 16 patients and FAPI-46 in 3 patients).

FIGURE 2.

Primary staging of a patient with PDAC. (A) Axial images of PDAC and liver in arterial (upper image) and venous (lower image) ceCT scan. (B) Mean intensity projection (MIP) images of 18F-FDG and FAPI PET/CT imaging. (C) Axial 18F-FDG and FAPI PET/CT images of same patient on level (blue line in A) of pancreatic tumor mass and another suspicious FAPI accumulation in projection on perihepatic lymph node. Metastatic situation, which had been revealed by FAPI PET/CT, was confirmed by biopsy of pulmonary lesion that was diagnosed as metastasis of known PDAC.

FIGURE 3.

Staging of patient with local recurrence of PDAC. (A) Mean intensity projection (MIP) image of FAPI PET/CT imaging. (B) Axial ceCT and FAPI PET/CT images of same patient on level of local recurrence (red line in A), 2 metastasis-suspicious intrahepatic foci (yellow line in A), and 3 suspicious osseous tracer accumulations (blue line in A). In contrast to CT imaging, FAPI PET/CT allows discrimination of metastatic lymph node from local recurrence mass (red arrow). FAPI PET/CT also revealed possible new liver (yellow arrows) and bone (blue arrows) metastases.

FIGURE 4.

(A and B) Average SUVmax and SUVmean 1 h after injection of 68Ga-labeled FAPI tracers in 8 PDAC and in accompanying pancreatitis in rest of pancreas. (C) Exemplary images of tumor-related (red arrow) and pancreatitis-related (yellow arrow) 68Ga-FAPI uptake 10, 60, and 180 min after application. (D) 68Ga-FAPI uptake 10, 60, and 180 min after application (SUVmax and SUVmean values) in PDAC lesions of 6 patients.