PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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. In vitro and in vivo 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.
UNASSIGNED: 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.
UNASSIGNED: [18F]F-FGFR1 showed high stability, affinity, specificity and good imaging capacity for FGFR1-overexpressing tumors in vivo, which provides new application potential in the visualization of FGFR1 expression in solid tumors.
UNASSIGNED: 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. In vitro and in vivo 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.
UNASSIGNED: 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.
UNASSIGNED: [18F]F-FGFR1 showed high stability, affinity, specificity and good imaging capacity for FGFR1-overexpressing tumors in vivo, which provides new application potential in the visualization of FGFR1 expression in solid tumors.
摘要：
■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，并代表了癌症治疗的新靶标。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功效。
■本研究首次提出了评估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）纯化合成了FGFR1靶向肽NOTA-PEG2-KAEWKSLGEEAWHSK，然后使用NOTA作为螯合剂用氟-18标记。进行了体外和体内实验以评估稳定性，探针的亲和力和特异性。在RT-112，A549，SNU-16和Calu-3异种移植物中，通过micro-PET/CT成像评估肿瘤靶向功效和生物分布。
■[18F]F-FGFR1的放射化学纯度为98.66％±0.30％（n=3），具有出色的稳定性。[18F]F-FGFR1在RT-112细胞系中的细胞摄取速率(FGFR1过表达)高于其他细胞系中的细胞摄取速率,并且可以通过存在过量的未标记的FGFR1肽而被阻断。Micro-PET/CT成像显示RT-112异种移植物中[18F]F-FGFR1的浓度显着，在非靶向器官和组织中没有摄取或摄取非常低，这表明[18F]F-FGFR1被FGFR1阳性肿瘤选择性吸收。
■[18F]F-FGFR1显示出高稳定性，亲和力,对体内FGFR1过表达肿瘤的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。
■本研究首次提出了评估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）纯化合成了FGFR1靶向肽NOTA-PEG2-KAEWKSLGEEAWHSK，然后使用NOTA作为螯合剂用氟-18标记。进行了体外和体内实验以评估稳定性，探针的亲和力和特异性。在RT-112，A549，SNU-16和Calu-3异种移植物中，通过micro-PET/CT成像评估肿瘤靶向功效和生物分布。
■[18F]F-FGFR1的放射化学纯度为98.66％±0.30％（n=3），具有出色的稳定性。[18F]F-FGFR1在RT-112细胞系中的细胞摄取速率(FGFR1过表达)高于其他细胞系中的细胞摄取速率,并且可以通过存在过量的未标记的FGFR1肽而被阻断。Micro-PET/CT成像显示RT-112异种移植物中[18F]F-FGFR1的浓度显着，在非靶向器官和组织中没有摄取或摄取非常低，这表明[18F]F-FGFR1被FGFR1阳性肿瘤选择性吸收。
■[18F]F-FGFR1显示出高稳定性，亲和力,对体内FGFR1过表达肿瘤的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。
