PET of EGFR expression with an 18F-labeled affibody molecule.
PET of EGFR expression with an 18F-labeled affibody molecule.
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DOI：
10.2967/jnumed.111.100842
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Cheng Z
中科院分区：
文献类型：
--
作者：
Miao Z;Ren G;Liu H;Qi S;Wu S;Cheng Z
表皮生长因子受体（Epidermal growth factor receptor， EGFR）在多种人类癌症中经常过表达，其表达与许多癌症类型的不良预后相关。然而，一种准确的无创成像EGFR在体内表达的技术在临床环境中是不可用的。在本研究中，一种抗EGFR的affigbody类似物Ac-Cys-ZEGFR:1907成功地通过18f位点特异性标记EGFR表达的PET。假体基团N-[2-（4- 18f -氟苯胺）乙基]马来酰亚胺（18F-FBEM）在温和条件（pH 7）下与Ac-Cys-ZEGFR:1907偶联，得到探针18F-FBEM- cys - zegfr:1907。采用A431癌细胞进行18F-FBEM-Cys-ZEGFR:1907与EGFR的结合亲和力和特异性试验。注射约2.0 MBq的18F-FBEM-Cys-ZEGFR:1907，并与未标记的Ac-Cys-ZEGFR:1907共注射3小时后，对EGFR过表达的6种小鼠肿瘤移植模型进行小动物PET和生物分布研究。对6种肿瘤模型进行18F-FBEM-Cys-ZEGFR:1907小动物PET定量与体外Western blot分析肿瘤EGFR表达的相关性研究。18F-FBEM-Cys-ZEGFR:1907在A431细胞中以低纳摩尔亲和力（37 nM）与EGFR结合。18F-FBEM-Cys-ZEGFR:1907在注射后3小时内迅速在肿瘤内积累，并在除肝和肾外的大部分正常器官中清除，从而获得良好的肿瘤与正常组织对比。A431肿瘤异种移植模型中,coinjection PET探测器Ac-Cys-ZEGFR 45μg: 1907能够提高肿瘤吸收(3.9和8.1的比例注入放射性剂量每克组织,在注射后3小时以内)和肿瘤成像对比度,而coinjection Ac-Cys-ZEGFR 500μg: 1907成功阻止了肿瘤吸收显著(8.1和1.0的比例注入放射性剂量每克组织,在注射后3小时以内,抑制88%,P < 0.05)。PET测定的注射后3 h肿瘤示踪剂摄取量与Western blot测定的EGFR表达水平呈正相关（P = 0.007, R = 0.59）。18F-FBEM-Cys-ZEGFR:1907是一种新型的基于蛋白支架的PET探针，用于肿瘤EGFR过表达的成像，其在体内区分EGFR高表达和低表达肿瘤的能力为未来的临床翻译带来了希望。
Epidermal growth factor receptor (EGFR) is often overexpressed in a variety of human cancers, and its expression is associated with poor prognosis for many cancer types. However, an accurate technique to noninvasively image EGFR expression in vivo is not available in the clinical setting. In this research, an Affibody analog, anti-EGFR Ac-Cys-ZEGFR:1907, was successfully site-specifically 18F-labeled for PET of EGFR expression. The prosthetic group N-[2-(4-18F-fluorobenzamido) ethyl] maleimide (18F-FBEM) was conjugated to Ac-Cys-ZEGFR:1907 under mild conditions (pH 7) to produce the probe 18F-FBEM-Cys-ZEGFR:1907. The binding affinity and specificity tests of 18F-FBEM-Cys-ZEGFR:1907 to EGFR were conducted using A431 cancer cells. Small-animal PET and biodistribution studies were conducted on various mice tumor xenograft models with EGFR overexpression (6 types) after injection of approximately 2.0 MBq of 18F-FBEM-Cys-ZEGFR:1907 with or without coinjection of unlabeled Ac-Cys-ZEGFR:1907 for up to 3 h after injection. A correlation study between 18F-FBEM-Cys-ZEGFR:1907 small- animal PET quantification and ex vivo Western blot analysis of tumor EGFR expression was conducted in those 6 types of tumor models. 18F-FBEM-Cys-ZEGFR:1907 binds to EGFR with low nanomolar affinity (37 nM) in A431 cells. 18F-FBEM-Cys-ZEGFR:1907 rapidly accumulated in the tumor and cleared from most of the normal organs except the liver and kidneys at 3 h after injection, allowing excellent tumor–to–normal tissue contrast to be obtained. In the A431 tumor xenograft model, coinjection of the PET probe with 45 μg of Ac-Cys-ZEGFR:1907 was able to improve the tumor uptake (3.9 vs. 8.1 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection) and tumor imaging contrast, whereas coinjection with 500 μg of Ac-Cys-ZEGFR:1907 successfully blocked the tumor uptake significantly (8.1 vs. 1.0 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection, 88% inhibition, P < 0.05). Moderate correlation was found between the tumor tracer uptake at 3 h after injection quantified by PET and EGFR expression levels measured by Western blot assay (P = 0.007, R = 0.59). 18F-FBEM-Cys-ZEGFR:1907 is a novel protein scaffold–based PET probe for imaging EGFR overexpression of tumors, and its ability to differentiate tumors with high and low EGFR expression in vivo holds promise for future clinical translation.
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影响因子：
11.2
作者：
Memon, Ashfaque A.;Jakobsen, Steen;Nexo, Ebba
通讯作者：
Nexo, Ebba
影响因子：
45.3
作者：
DiGiovanna, MP;Stern, DF;Thor, AD
通讯作者：
Thor, AD
影响因子：
4.7
作者：
Ahlgren, Sara;Orlova, Anna;Tolmachev, Vladimir
通讯作者：
Tolmachev, Vladimir
DOI：
10.1007/s00259-007-0658-0
发表时间：
2008-05
影响因子：
9.1
作者：
Kramer-Marek, Gabriela;Kiesewetter, Dale O.;Martiniova, Lucia;Jagoda, Elaine;Lee, Sang Bong;Capala, Jacek
通讯作者：
Capala, Jacek
DOI：
10.1007/s00259-006-0361-6
发表时间：
2007-06-01
影响因子：
9.1
作者：
Cai, Weibo;Chen, Kai;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan