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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 (SUV max , SUV mean); 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 Log2 TLF 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 Log2 TLF were associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016 and Log2 TLF 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 SUV max , MTV, and TLF were associated with good treatment response (all P <0.05). ΔMTV, ΔTLF and ΔSUV max 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. [ABSTRACT FROM AUTHOR]

Tumor-associated fibroblasts (CAF) are expressed in tumor stroma and play an important role in tumor proliferation, invasion, metastasis and drug resistance. Fibroblast activating protein inhibitor (FAPI) is a new type of PET tracer, which can be used to evaluate the expression of FAP in CAF. We aimed to explore whether biological distribution of [18F]Alf-NOTA-FAPI-04-positron emission tomography/computed tomography (PET/CT) reflected the expression of CAF related markers and immune markers in cancer tissues based on pathology. The study included 20 patients with rectal cancer who underwent [18F] AlF-NOTAFAPI-04PET/CT scans 3 days before surgery. The following FAPI uptake variables were generated using nuclear medicine information system: maximum standardized uptake value [SUVmax], SUVpeak, SUVmean, and total lesion glycolysis (TLG). The tumor specimens were stained with immunohistochemistry after operation, including CAF related markers, FAP, S100A4, Vimentin, PDGFRα/β and α-SMA as well as including immune markers, CD8 and CD163. FAPI uptake variables including SUVmax, SUVmean, SUVpeak, TLG were positively correlated with FAP (all p < 0.05), α-SMA (all p < 0. 05), Vimentin (all p < 0. 05), S100A4 (all p < 0.05) and PDGFRα/β, all p < 0.001). FAPI uptake variables were negatively correlated with CD8 (all P < 0.05) and CD163 (all p < 0.05). There were significant differences between T stages and SUVmax as well as SUVmean (all p < 0.05). [18F] AlF-NOTAFAPI-04PET/CT uptake variables can reflect the expression of CAF-related markers and correlated with immune markers, which may have the potential to identify high-risk patients for early intensifying treatment and identify patients for receiving immunotherapy. [ABSTRACT FROM AUTHOR]