PET imaging of EGFR expression using an (18)F-labeled RNA aptamer.
PET imaging of EGFR expression using an (18)F-labeled RNA aptamer.
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使用 F-18 标记的 RNA 适体对 EGFR 表达进行 PET 成像
DOI：
10.1007/s00259-018-4105-1
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发表时间：
2019-04
影响因子：
9.1
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Cheng S;Jacobson O;Zhu G;Chen Z;Liang SH;Tian R;Yang Z;Niu G;Zhu X;Chen X
表皮生长因子受体（EGFR）是多种癌症类型的治疗诊断生物标志物。本研究的目的是开发一种18F放射性标记的EGFR靶向RNA适体，并研究其在异种移植模型中可视化和定量EGFR的能力。采用生物膜干涉法检测经炔基修饰的EGFR适体MinE 07（记为ME 07）与重组人野生型EGFR蛋白和突变型EGFR vIII蛋白的结合亲和力。Cy 5缀合的ME 07用于流式细胞术和免疫荧光染色，并且Alexa Fluor 488标记的EGFR抗体（ab 193244）用作对照。以18 F-氟苯甲酰基（FB）叠氮化物为合成子，通过点击化学法合成了18 F-FB-ME 07，并研究了18 F-FB-ME 07的细胞摄取和内化特性。在三种肿瘤模型中进行18F-FB-ME 07的静态PET扫描、60 min动态扫描和生物分布研究。ME 07对wtEGFR和EGFRvIII蛋白的Kd值分别为0.3 nM和271 nM。A431、U87 MG和HCT-116细胞显示与Cy 5-ME 07的强、弱和阴性结合，这与这些细胞中的EGFR表达水平一致。A431、U87 MG和HCT-116细胞中18 F-FB-ME 07的细胞摄取峰值分别为添加剂量的2.86%、2.19%和0.88%。18F-FB-ME 07在这些细胞中的平均内化分别为总累积放射性的60.02%、53.1%和52.8%。在静态PET成像中，尽管在肝脏和肾脏中具有高摄取，但18F-FB-ME 07在A431肿瘤中显示出合理的积累（在注射后30分钟为1.02 ± 0.13%ID/g）。值得注意的是，A431异种移植物中18F-FB-ME 07的摄取显著高于U87 MG和HCT-116异种移植物中的摄取。在A431异种移植小鼠中，肿瘤/血液比为3.89，肿瘤/肌肉比达到8.65。我们首次产生了适体衍生的EGFR靶向PET示踪剂18F-FB-ME 07，其在表达不同水平EGFR的小鼠肿瘤模型中显示出高度选择性靶向能力。我们的研究结果表明，18F-FB-ME 07是一个潜在的EGFR靶向分子成像探针，用于未来的临床翻译。
Epidermal growth factor receptor (EGFR) is a theranostic biomarker for a variety of cancer types. The aim of the present study was to develop an 18F radiolabeled EGFR targeting RNA aptamer, and to investigate its ability to visualize and quantify EGFR in xenograft models. Biolayer 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. 18F-Fluorobenzoyl (FB) azide was employed as a synthon to produce 18F-FB-ME07 via click chemistry, and the cellular uptake and internalization characteristics of 18F-FB-ME07 were investigated. Static PET scans, 60-min dynamic scans and biodistribution study of 18F-FB-ME07 were performed in three types of tumor models. The Kd values of ME07 to wtEGFR and EGFRvIII proteins were 0.3 nM and 271 nM, 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 18F-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 18F-FB-ME07 in these cells were 60.02%, 53.1% and 52.8% of the total accumulated radioactivity. In static PET imaging, despite of high uptake in the liver and kidneys, 18F-FB-ME07 showed reasonable accumulation in A431 tumors (1.02 ± 0.13 %ID/g at 30 min after injection). Of note, the uptake of 18F-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. We for the first time generated an aptamer-derived EGFR targeting PET tracer 18F-FB-ME07, which showed highly selective targeting ability in mouse tumor models expressing different levels of EGFR. Our results suggest that 18F-FB-ME07 is a potential EGFR targeting molecular imaging probe for future clinical translation.
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DOI：
10.1007/s00259-009-1158-1
发表时间：
2009-09
影响因子：
9.1
作者：
Niu, Gang;Li, Zibo;Cao, Qizhen;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
62.1
作者：
Tan W;Donovan MJ;Jiang J
通讯作者：
Jiang J
影响因子：
3.1
作者：
Da Pieve, Chiara;Perkins, Alan C.;Missailidis, Sotiris
通讯作者：
Missailidis, Sotiris
影响因子：
16.6
作者：
Rotstein, Benjamin H.;Stephenson, Nickeisha A.;Liang, Steven H.
通讯作者：
Liang, Steven H.
影响因子：
51.1
作者：
Pirker, Robert;Pereira, Jose R.;O'Byrne, Kenneth J.
通讯作者：
O'Byrne, Kenneth J.