Comparative study of [<sup>18</sup>F]AlF-NOTA-FAPI-RGD and [<sup>18</sup>F]FDG/[<sup>18</sup>F]AlF-NOTA-FAPI-04 PET/CT in renal cell carcinoma
Authors: Haiyan Gao, Zhiwei Ma, Ziyang Zhu, Zhichuan Yang, Bo Chen, Xiaoming Wu, Vivianne Jakobsson, Yujiao Deng, Hao Wang, Wei Zhang, Jingjing Zhang
Journal: Theranostics (2025)

Renal cell carcinoma (RCC) is a significant global health concern, and the early diagnosis and accurate staging of clear cell renal cell carcinoma (ccRCC) remain major challenges. [18F]FDG PET/CT is not ideal for diagnosing ccRCC due to the low glucose metabolism potential of cancer cells. Both fibroblast activation protein (FAP) and the angiogenic integrin αvβ3 receptor are closely linked to the pathogenesis and progression of ccRCC. The aim of this study is to evaluate a novel radiopharmaceutical [18F]AlF-NOTA-FAPI-RGD (denoted as [18F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both FAP and integrin αvβ3, and to compare the diagnostic value of [18F]AlF-LNC1007 with [18F]FDG and [18F]AlF-NOTA-FAPI-04 PET/CT in RCC. Materials and Methods: A total of 35 participants, highly suspected to have RCC, were recruited. [18F]AlF-LNC1007 and [18F]AlF-NOTA-FAPI-04/[18F]FDG scans were performed at least one day apart, and both were completed within one week. The Wilcoxon signed-rank test or paired t-test was used to assess differences in tumor uptake and TBR (tumor-to-background ratio) between [18F]AlF-LNC1007 and the other two imaging agents. The Spearman correlation coefficient was used to evaluate the correlation between tumor uptake and the expression of FAP and αvβ3. Results: The detection rate, sensitivity, and positive predictive value (PPV) of [18F]AlF-LNC1007 for RCC primary lesions were significantly higher than those of [18F]FDG, at 91% vs. 76%, 100% vs. 85%, and 91% vs. 87%, respectively. Obvious advantages were also seen in metastatic lesions at 94% vs. 34%, 94% vs. 29%, and 100% vs. 100%. Compared to [18F]AlF-NOTA-FAPI-04, the corresponding detection rate, sensitivity, and PPV were 98% vs. 90%, 100% vs. 92%, and 98% vs. 98% for primary lesions, and 89% vs. 78%, 89% vs. 93%, and 100% vs. 82% for metastatic lesions. The uptake and TBR of [18F]AlF-LNC1007 in both primary and metastatic lesions were significantly higher than those of [18F]FDG (all P < 0.001). The uptake of [18F]AlF-LNC1007 showed a moderate to high positive correlation with the expression levels of αvβ3 and the combined expression of FAP and αvβ3 (r = 0.756, P = 0.0003; r = 0.678, P = 0.0002) and a low positive correlation with FAP expression alone (r = 0.389, P = 0.014). The uptake of [18F]AlF-NOTA-FAPI-04 showed a low to moderate positive correlation with FAP expression and the combined expression of FAP and αvβ3 (r = 0.570, P = 0.0002; r = 0.408, P = 0.010), and no correlation with αvβ3 expression alone (r = 0.262, P = 0.107). Conclusion: [18F]AlF-LNC1007 demonstrated significantly higher diagnostic efficacies and uptake in primary and metastatic renal cell carcinoma (RCC) compared to FDG PET/CT. Additionally, [18F]AlF-LNC1007 exhibited higher diagnostic efficacies and uptake in primary RCC than [18F]AlF-NOTA-FAPI-04 PET/CT. While these findings suggest potential diagnostic advantages, further studies are needed to fully evaluate its diagnostic efficacy compared to the standard of treatment.