Chen Yang, Han Jingya, Zhao Yan, Zhao Xinming, Zhao Mengmeng, Zhang Jingmian, Wang Jianfang
Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Front Oncol. 2023 Apr 27;13:1047080. doi: 10.3389/fonc.2023.1047080. eCollection 2023.
The fibroblast growth factor receptor (FGFR) family is highly expressed in a variety of tumor types and represents a new target for cancer therapy. Different FGFR subtype aberrations have been found to exhibit highly variable sensitivity and efficacy to FGFR inhibitors.
The present study is the first to suggest an imaging method for assessing FGFR1 expression. The FGFR1-targeting peptide NOTA-PEG2-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-pressure liquid chromatography (HPLC) purification and then labeled with fluorine-18 using NOTA as a chelator. and experiments were conducted to evaluate the stability, affinity and specificity of the probe. Tumor targeting efficacy and biodistribution were evaluated by micro-PET/CT imaging in RT-112, A549, SNU-16 and Calu-3 xenografts.
The radiochemical purity of [18F]F-FGFR1 was 98.66% ± 0.30% (n = 3) with excellent stability. The cellular uptake rate of [18F]F-FGFR1 in the RT-112 cell line (FGFR1 overexpression) was higher than that in the other cell lines and could be blocked by the presence of excess unlabeled FGFR1 peptide. Micro-PET/CT imaging revealed a significant concentration of [18F]F-FGFR1 in RT-112 xenografts with no or very low uptake in nontargeted organs and tissues, which demonstrated that [18F]F-FGFR1 was selectively taken up by FGFR1-positive tumors.
[18F]F-FGFR1 showed high stability, affinity, specificity and good imaging capacity for FGFR1-overexpressing tumors , which provides new application potential in the visualization of FGFR1 expression in solid tumors.
成纤维细胞生长因子受体（FGFR）家族在多种肿瘤类型中高表达，是癌症治疗的新靶点。已发现不同的FGFR亚型畸变对FGFR抑制剂表现出高度可变的敏感性和疗效。
本研究首次提出一种评估FGFR1表达的成像方法。通过手动固相肽合成和高压液相色谱（HPLC）纯化合成靶向FGFR1的肽NOTA-PEG2-KAEWKSLGEEAWHSK，然后以NOTA作为螯合剂用氟-18进行标记。进行体外和体内实验以评估探针的稳定性、亲和力和特异性。通过微型PET/CT成像在RT-112、A549、SNU-16和Calu-3异种移植瘤中评估肿瘤靶向疗效和生物分布。
[18F]F-FGFR1的放射化学纯度为98.66%±0.30%（n = 3），稳定性良好。[18F]F-FGFR1在RT-112细胞系（FGFR1过表达）中的细胞摄取率高于其他细胞系，并且可被过量未标记的FGFR1肽阻断。微型PET/CT成像显示，[18F]F-FGFR1在RT-112异种移植瘤中显著浓聚，在非靶向器官和组织中摄取极少或无摄取，这表明[18F]F-FGFR1被FGFR1阳性肿瘤选择性摄取。
[18F]F-FGFR1对FGFR1过表达肿瘤显示出高稳定性、亲和力、特异性和良好的成像能力，为实体瘤中FGFR1表达的可视化提供了新的应用潜力。
