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BACKGROUND: Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI-avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann-Whitney U test, and McNemar's test was used to assess the diagnostic accuracy between the two techniques. RESULTS: In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. CONCLUSIONS: [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. TRIAL REGISTRATION: Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.

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Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized by hypometabolism. Here, we investigated 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18F-FDG. Methods: Sixty-two PDAC patients underwent 18F-FAPI-04 PET/CT and 18F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUVmax of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18F-FAPI-04 PET/CT identified all patients with PDAC; 18F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18F-FAPI-04 PET/CT than in 18F-FDG PET/CT in primary tumors (10.63 vs. 2.87, P < 0.0001), LN metastasis (2.90 vs. 1.43, P < 0.0001), and DM (liver, 6.11 vs. 3.10, P = 0.002; peritoneal, 4.70 vs. 2.08, P = 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for 18F-FAPI-04 PET/CT than for 18F-FDG PET/CT (P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18F-FAPI-04 PET/CT compared with 18F-FDG PET/CT. A high SUVmax of the primary tumor did not correlate with treatment response for either 18F-FAPI-04 or 18F-FDG. Conclusion: 18F-FAPI-04 PET/CT performed better than 18F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.

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Purpose: This prospective study examined whether metabolism parameters obtained using the tracer 18F-AlFNOTA-fibroblast activation protein inhibitor (FAPI)-04 (denoted as 18F-FAPI-04) in positron emission tomography/computed tomography (PET/CT) can predict programmed death ligand-1 (PD-L1) expression in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Patients and methods: The 24 enrolled LA-ESCC patients underwent an 18F-FAPI-04 PET/CT scan. The maximum, mean, peak and standard deviation standard uptake values (SUVmax, SUVmean, SUVpeak and SUVsd), metabolic tumor volume (MTV), and total lesion FAP (TLF) expression of the primary tumor were collected. Additionally, we evaluated PD-L1 expression on cancer cells by immunohistochemistry and immunofluorescence methods. Patients were divided into negative and positive expressions according to the expression of PD-L1 (CPS < 10 and CPS ≥ 10), and the variables were compared between the two groups. Results: The SUVmax, SUVmean, SUVpeak and SUVsd were significantly higher in patients with positive expression than in negative expression (all p < 0.05). Receiver operating characteristic curve analysis identified SUVmean (area under the curve [AUC] = 0.882, p = 0.004), SUVsd (AUC = 0.874, p = 0.005), SUVpeak (AUC = 0.840, p = 0.010) and SUVmax (AUC = 0.765, p = 0.045) as significant predictors of the PD-L1 positive expression, with cutoff values of 9.67, 1.90, 9.67 and 13.71, respectively. On univariate logistic regression analysis, SUVmean (p = 0.045), SUVsd (p = 0.024), and SUVpeak (p = 0.031) were significantly correlated with the PD-L1 positive expression. On multivariable logistic regression analysis, SUVsd (p = 0.035) was an optimum predictor factor for PD-L1 positive expression. Conclusion: 18F-FAPI-04 PET/CT parameters, including SUVmean, SUVpeak, and SUVsd, correlated with PD-L1 expression in patients with LA-ESCC, and thus SUVsd was an optimum predictor for PD-L1 positive expression, which could help to explore the existence of immune checkpoints and select ESCC candidates for immunotherapy.

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