Gao Haiyan, Ma Zhiwei, Zhu Ziyang, Yang Zhichuan, Chen Bo, Wu Xiaoming, Jakobsson Vivianne, Deng Yujiao, Wang Hao, Zhang Wei, Zhang Jingjing
Department of Nuclear Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Department of Urology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Theranostics. 2025 Apr 21;15(12):5790-5800. doi: 10.7150/thno.113070. eCollection 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. [F]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 αβ receptor are closely linked to the pathogenesis and progression of ccRCC. The aim of this study is to evaluate a novel radiopharmaceutical [F]AlF-NOTA-FAPI-RGD (denoted as [F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both FAP and integrin αβ, and to compare the diagnostic value of [F]AlF-LNC1007 with [F]FDG and [F]AlF-NOTA-FAPI-04 PET/CT in RCC. : A total of 35 participants, highly suspected to have RCC, were recruited. [F]AlF-LNC1007 and [F]AlF-NOTA-FAPI-04/[F]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 [F]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 αβ The detection rate, sensitivity, and positive predictive value (PPV) of [F]AlF-LNC1007 for RCC primary lesions were significantly higher than those of [F]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 [F]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 [F]AlF-LNC1007 in both primary and metastatic lesions were significantly higher than those of [F]FDG (all P < 0.001). The uptake of [F]AlF-LNC1007 showed a moderate to high positive correlation with the expression levels of αβ and the combined expression of FAP and αβ (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 [F]AlF-NOTA-FAPI-04 showed a low to moderate positive correlation with FAP expression and the combined expression of FAP and αβ (r = 0.570, P = 0.0002; r = 0.408, P = 0.010), and no correlation with αβ expression alone (r = 0.262, P = 0.107). [F]AlF-LNC1007 demonstrated significantly higher diagnostic efficacies and uptake in primary and metastatic renal cell carcinoma (RCC) compared to FDG PET/CT. Additionally, [F]AlF-LNC1007 exhibited higher diagnostic efficacies and uptake in primary RCC than [F]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.
肾细胞癌（RCC）是一个重大的全球健康问题，透明细胞肾细胞癌（ccRCC）的早期诊断和准确分期仍然是主要挑战。由于癌细胞的葡萄糖代谢潜力低，[F]FDG PET/CT对于ccRCC的诊断并不理想。成纤维细胞活化蛋白（FAP）和血管生成整合素αβ受体都与ccRCC的发病机制和进展密切相关。本研究的目的是评估一种新型放射性药物[F]AlF-NOTA-FAPI-RGD（记为[F]AlF-LNC1007），一种同时靶向FAP和整合素αβ的双靶点异二聚体示踪剂，并比较[F]AlF-LNC1007与[F]FDG以及[F]AlF-NOTA-FAPI-04 PET/CT在RCC中的诊断价值。总共招募了35名高度怀疑患有RCC的参与者。[F]AlF-LNC1007和[F]AlF-NOTA-FAPI-04/[F]FDG扫描至少间隔一天进行，且均在一周内完成。采用Wilcoxon符号秩检验或配对t检验来评估[F]AlF-LNC1007与其他两种成像剂之间肿瘤摄取和TBR（肿瘤与背景比值）的差异。采用Spearman相关系数评估肿瘤摄取与FAP和αβ表达之间的相关性。[F]AlF-LNC1007对RCC原发灶的检出率、敏感性和阳性预测值（PPV）显著高于[F]FDG，分别为91%对76%、100%对85%、91%对87%。在转移灶中也有明显优势，分别为94%对34%、94%对29%、100%对100%。与[F]AlF-NOTA-FAPI-04相比，原发灶的相应检出率、敏感性和PPV分别为98%对90%、100%对92%、98%对98%，转移灶分别为89%对78%、89%对93%、100%对82%。[F]AlF-LNC1007在原发灶和转移灶中的摄取和TBR均显著高于[F]FDG（所有P<0.001）。[F]AlF-LNC1007的摄取与αβ的表达水平以及FAP和αβ的联合表达呈中度至高度正相关（r=0.756，P=0.0003；r=0.678，P=0.0002），与单独的FAP表达呈低度正相关（r=0.389，P=0.014）。[F]AlF-NOTA-FAPI-04的摄取与FAP表达以及FAP和αβ的联合表达呈低度至中度正相关（r=0.570，P=0.0002；r=0.408，P=0.010），与单独的αβ表达无相关性（r=0.262，P=0.107）。与FDG PET/CT相比，[F]AlF-LNC1007在原发性和转移性肾细胞癌（RCC）中显示出显著更高的诊断效能和摄取。此外，[F]AlF-LNC1007在原发性RCC中比[F]AlF-NOTA-FAPI-04 PET/CT表现出更高的诊断效能和摄取。虽然这些发现表明了潜在的诊断优势，但与治疗标准相比，仍需要进一步研究以充分评估其诊断效能。
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