Jia Fan, Hou Dayong, Zhang Han, You Huihui, Cheng Liang, Liu Wei, Zhao Yue, Yang Xinyue, Zhou Xinglu, Yu Miao, Hu Geng, Guo Chenxu, Meng Hongxue, Xu Wanhai, Wang Kezheng
Department of PET-CT/MRI, NHC Key Laboratory of Molecular Probe and Targeted Theranostics, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Eur J Nucl Med Mol Imaging. 2025 Sep 9. doi: 10.1007/s00259-025-07549-9.
CXCR4 and integrin αβ play important roles in tumor biology and are highly expressed in multiple types of tumors. This study aimed to synthesize, preclinically evaluate, and clinically validate a novel dual-targeted PET imaging probe Ga-pentixafor-c(RGDfK) for its potential in imaging tumors.
The effects of Ga-pentixafor-c(RGDfK) on cell viability, targeting specificity, and affinity were assessed in the U87MG cells. Micro-PET/CT imaging and biodistribution studies were conducted in U87MG tumor-bearing BALB/c nude mice to evaluate the probe's in vivo pharmacokinetics. A prospective analysis was conducted on patients who underwent both Ga-pentixafor-c(RGDfK) PET/CT and F-FDG PET/CT. The results obtained from the two imaging modalities were compared.
In vitro, Ga-pentixafor-c(RGDfK) showed higher uptake activity, targeting specificity, and affinity in U87MG cells than Ga-pentixafor. In vivo, tumor uptake was higher than in normal tissues (P < 0.05), with renal excretion and low hepatobiliary excretion. Clinical results indicated that Ga-pentixafor-c(RGDfK) PET/CT had higher sensitivity, specificity, and accuracy in diagnosing primary and metastatic lesions compared to F-FDG PET/CT (93.1% vs. 74.7%, 79.2% vs. 62.5%, 90.1% vs. 72.1%, and 93.2% vs. 74.5%, 84.7% vs. 78%, 89.7% vs. 75.9%). The tumor-to-background ratio (TBR) at 120 min delayed scanning was significantly higher than at 60 min (P < 0.05).
Ga-pentixafor-c(RGDfK) PET/CT demonstrated good safety and clinical feasibility in diagnosing tumors, particularly in differentiating benign and malignant lesions when F-FDG PET/CT results are uncertain.
CXCR4和整合素αβ在肿瘤生物学中发挥重要作用，且在多种类型肿瘤中高表达。本研究旨在合成、临床前评估并临床验证一种新型双靶点PET成像探针Ga-喷替沙福-c(RGDfK)在肿瘤成像方面的潜力。
在U87MG细胞中评估Ga-喷替沙福-c(RGDfK)对细胞活力、靶向特异性和亲和力的影响。在荷U87MG肿瘤的BALB/c裸鼠中进行微型PET/CT成像和生物分布研究，以评估该探针的体内药代动力学。对接受Ga-喷替沙福-c(RGDfK)PET/CT和F-FDG PET/CT检查的患者进行前瞻性分析。比较两种成像方式获得的结果。
在体外，Ga-喷替沙福-c(RGDfK)在U87MG细胞中表现出比Ga-喷替沙福更高的摄取活性、靶向特异性和亲和力。在体内，肿瘤摄取高于正常组织(P < 0.05)，经肾脏排泄，肝胆排泄较少。临床结果表明，与F-FDG PET/CT相比，Ga-喷替沙福-c(RGDfK)PET/CT在诊断原发性和转移性病变方面具有更高的敏感性、特异性和准确性(93.1%对74.7%，79.2%对62.5%，90.1%对72.1%，以及93.2%对74.5%，84.7%对78%，89.7%对75.9%)。120分钟延迟扫描时的肿瘤与本底比值(TBR)显著高于60分钟时(P < 0.05)。
Ga-喷替沙福-c(RGDfK)PET/CT在肿瘤诊断中显示出良好的安全性和临床可行性，特别是在F-FDG PET/CT结果不确定时用于鉴别良性和恶性病变。
