ObjectiveEpidermal growth factor receptor (EGFR) is a theranostic biomarker for a variety of cancer types. The aim of the present study was to develop an F-18 radiolabeled EGFR targeting RNA aptamer, and to investigate its ability to visualize and quantify EGFR in xenograft models.MethodsBiolayer interferometry binding assay was used to detect the binding affinity of the alkyne-modified EGFR aptamer MinE07 (denoted as ME07) with recombinant human wild-type EGFR protein and the mutant EGFRvIII protein. Cy5-conjugated ME07 was used for flow cytometry and immunofluorescence staining, and an Alexa Fluor 488-labeled EGFR antibody (ab193244) was used as a control. F-18-Fluorobenzoyl (FB) azide was employed as a synthon to produce F-18-FB-ME07 via click chemistry, and the cellular uptake and internalization characteristics of F-18-FB-ME07 were investigated. Static PET scans, 60-min dynamic scans, and biodistribution study of F-18-FB-ME07 were performed in three types of tumor models.ResultsThe K-d values of ME07 to wtEGFR and EGFRvIII proteins were 0.3nM and 271nM respectively. The A431, U87MG, and HCT-116 cells showed strong, weak, and negative binding with Cy5-ME07, which is consistent with EGFR expression level in these cells. Peak cell uptake values of F-18-FB-ME07 in A431, U87MG and HCT-116 cells were 2.86%, 2.19% and 0.88% of the added dose respectively. The mean internalization of F-18-FB-ME07 in these cells were 60.02%, 53.1%, and 52.8% of the total accumulated radioactivity. In static PET imaging, despite high uptake in the liver and kidneys, F-18-FB-ME07 showed reasonable accumulation in A431 tumors (1.020.13 %ID/g at 30min after injection). Of note, the uptake of F-18-FB-ME07 in A431 xenografts was significantly higher than that in U87MG and HCT-116 xenografts. In A431 xenografted mice, the tumor/blood ratio was 3.89 and the tumor/muscle ratio reached 8.65.ConclusionsWe for the first time generated an aptamer-derived EGFR targeting PET tracer F-18-FB-ME07, which showed highly selective targeting ability in mouse tumor models expressing different levels of EGFR. Our results suggest that F-18-FB-ME07 is a potential EGFR targeting molecular imaging probe for future clinical translation.
基金：
Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Natural Science Foundation of China [81671718, 81271600]; Natural Science Foundation of Hubei Province of China [2016CFB687]; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZIAEB000073] Funding Source: NIH RePORTER
第一作者单位：[1]Huazhong Univ Sci & Technol, Dept Nucl Med & PET, Tongji Hosp, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430000, Hubei, Peoples R China[2]Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 35A Convent Dr Rm GD959, Bethesda, MD 20892 USA
通讯作者：
推荐引用方式(GB/T 7714)：
Cheng Siyuan,Jacobson Orit,Zhu Guizhi,et al.PET imaging of EGFR expression using an 18F-labeled RNA aptamer[J].EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING.2019,46(4):948-956.doi:10.1007/s00259-018-4105-1.
APA：
Cheng, Siyuan,Jacobson, Orit,Zhu, Guizhi,Chen, Zhen,Liang, Steve H....&Chen, Xiaoyuan.(2019).PET imaging of EGFR expression using an 18F-labeled RNA aptamer.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,46,(4)
MLA：
Cheng, Siyuan,et al."PET imaging of EGFR expression using an 18F-labeled RNA aptamer".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 46..4(2019):948-956
医学