Comparative Study of [¹⁸F]AlF-LNC1007, [¹⁸F]FDG, and [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in Breast Cancer Diagnosis: A Methodological Exploration and Analytical Insight

<b>Objective:</b> To compare the diagnostic value of [¹⁸F]AlF-LNC1007, [¹⁸F]FDG, and [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in breast cancer. <b>Methods:</b> 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 SUV_max 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 SUV_max or TBR. Diagnostic efficacy for lymph node metastasis was evaluated using receiver operating characteristic (ROC) analysis. <b>Results:</b> Compared to [¹⁸F]FDG, [¹⁸F]AlF-LNC1007 had a higher positive predictive value (100% vs 91%, <i>P</i> = 0.0004) in lymph node metastases (42 vs 46) and higher sensitivity (100 vs 76%, <i>P</i> = 0.0003) in bone metastases (33 vs 25) but lower sensitivity (93 vs 100%, <i>P</i> = 0.001) in liver metastases. Apart from liver metastases, [¹⁸F]AlF-LNC1007 PET/CT had higher SUV_max 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%, <i>P</i> = 0.0003) but had lower SUV_max(<i>P</i> < 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, <i>P</i> = 0.001). The comparison of lymph node detection efficacy between [¹⁸F]AlF-LNC1007 and [¹⁸F]FDG PET/CT showed significant differences in SUV_max 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 <i>P</i> < 0.001). <b>Conclusion:</b> [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.