Objective: To compare the diagnostic value of [18F]AlF-LNC1007, [18F]FDG, and [18F]AlF-NOTA-FAPI-04 PET/CT in breast cancer. Methods: 33 patients with highly suspected or already diagnosed but untreated breast cancer were enrolled in the study and underwent [18F]AlF-LNC1007 (30 patients), [18F]FDG (22 patients), and [18F]AlF-NOTA-FAPI-04 (8 patients) PET/CT. Quantitative measurements included the SUVmax and tumor-to-background ratio (TBR) for all lesions and background tissues. The Chi-square test was used for intergroup diagnostic efficacy, and the Wilcoxon test was used for intergroup SUVmax or TBR. Diagnostic efficacy for lymph node metastasis was evaluated using receiver operating characteristic (ROC) analysis. Results: Compared to [18F]FDG, [18F]AlF-LNC1007 had a higher positive predictive value (100% vs 91%, P = 0.0004) in lymph node metastases (42 vs 46) and higher sensitivity (100 vs 76%, P = 0.0003) in bone metastases (33 vs 25) but lower sensitivity (93 vs 100%, P = 0.001) in liver metastases. Apart from liver metastases, [18F]AlF-LNC1007 PET/CT had higher SUVmax in primary tumor and other metastases, with no statistical difference in TBR. Compared to [18F]AlF-NOTA-FAPI-04 PET/CT, [18F]AlF-LNC1007 had less false-positive and a higher positive predictive value in bone metastases (99 vs 95%, P = 0.0003) but had lower SUVmax(P < 0.01) in all primary and metastases lesions. The TBR difference between [18F]AlF-LNC1007 and [18F]AlF-NOTA-FAPI-04 was statistically significant only in bone metastases (5.97 vs 5.02, P = 0.001). The comparison of lymph node detection efficacy between [18F]AlF-LNC1007 and [18F]FDG PET/CT showed significant differences in SUVmax cutoff values for diagnosing lymph node metastases (2.62 vs 3.90), sensitivity (95.2% vs 66.67), and specificity (100% vs 85.00) (all P < 0.001). Conclusion: [18F]AlF-LNC1007 demonstrated superior efficacy compared to [18F]FDG and [18F]AlF-NOTA-FAPI-04 and higher uptake than [18F]FDG in primary tumor, lymph node and bone metastases, and higher TBR than [18F]AlF-NOTA-FAPI-04, especially in bone metastases. [18F]AlF-LNC1007 also showed high specificity in differentiating inflammatory and metastatic lymph nodes.
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