18F-AlF-NOTA-FAPI-04 PET/CT can Predict Treatment Response and Survival in Patients with Inoperable Pancreatic Adenocarcinoma

Abstract

We investigated whether uptake of 18F-AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic adenocarcinoma (PAAD). We prospectively evaluated 47 patients with histopathologically confirmed primary PAAD and pretreatment 18F-FAPI PET/CT scans to determine uptake of fibroblast activation protein (FAP) and compare the findings with those from blood tests and immunohistochemically stained tumor specimens. Cox regression and Kaplan-Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cutoff points for distinguishing patients according to good response vs poor response per RECIST v. 1.1. The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean); metabolic tumor volume (MTV); and total lesion FAP expression (TLF) were positively correlated with cancer-associated fibroblast (CAF) markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P<0.05). MTV and Log2TLF were associated with survival in patients with inoperable PAAD (all P<0.05). Analyses controlling for sex, age, cTNM, and performance status showed that MTV and Log2TLF were associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016 and Log2TLF HR = 4.093, P = 0.003). ROC cutoff analysis indicated that elevated MTV and TLF were associated with poorer survival. Greater changes from before to after chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P<0.05). ΔMTV, ΔTLF and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan-Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cutoff values (based on medians) of -4.95 for ΔMTV (HR = 8.09, P = 0.013) and -77.83 for ΔTLF (HR = 4.62, P = 0.012). Higher baseline MTV on 18F-FAPI-04 PET/CT scans was associated with poorer survival in patients with inoperable PAAD. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PAAD who are at high risk of disease progression.