Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging.
Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging.
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作者：
Wang H;Gao H;Guo N;Niu G;Ma Y;Kiesewetter DO;Chen X
Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Single-chain (sc)-VEGF protein containing an N-terminal Cys-tag has been designed for site-specific modification with a variety of imaging and therapeutic moieties. Site-specific labeling of scVEGF with thiol-reactive prosthetic group, N-[2-(4-18F-fluorobenzamido) ethyl] maleimide ([18F]FBEM) for positron emission tomography (PET) imaging of VEFGR may provide a new tracer which has great potential for clinical translation. Methods: [18F]FBEM-scVEGF was synthesized by site-specific conjugation of 18F-FBEM to a thiol group in Cys-tag of scVEGF at room temperature. The functional activity after labeling was tested by immunofluorescence staining, cellular uptake and efflux. The tumor targeting and in vivo properties were evaluated by biodistribution and microPET studies in tumor-bearing mice. Results: The radiolabeling yield and specific activity of [18F]FBEM-scVEGF were 20.6 ± 15.1% (based on starting [18F]FBEM, uncorrected, n = 5) and 58.8 ± 12.4 GBq/µmol, respectively. Noninvasive microPET and direct tissue sampling experiments demonstrated that [18F]FBEM-scVEGF had VEGFR specific tumor uptake in MDA-MB-435, U87MG and 4T1 xenograft models. The optimal tumor uptake was achieved at 2 h p.i., which can be partially, but significantly blocked by co-injection of non-labeled scVEGF protein. Overall, [18F]FBEM-scVEGF showed VEGFR specific tumor uptake. Conclusion: The scVEGF was site-specifically labeled with 18F via [18F]FBEM prosthetic group and the tracer [18F]FBEM-scVEGF exhibited high receptor binding affinity and tumor targeting efficacy. Further study of [18F] FBEM-scVEGF to evaluate angiogenesis in cancer and other disease types is warranted.
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影响因子：
6.7
作者：
Anderson CR;Rychak JJ;Backer M;Backer J;Ley K;Klibanov AL
通讯作者：
Klibanov AL
雷珠单抗和贝伐单抗的持久争议
影响因子：
12.4
作者：
Zou L;Lai H;Zhou Q;Xiao F
通讯作者：
Xiao F
DOI：
10.1007/s00259-009-1111-3
发表时间：
2009-08-01
影响因子：
9.1
作者：
Samen, Erik;Thorell, Jan-Olov;Stone-Elander, Sharon
通讯作者：
Stone-Elander, Sharon
影响因子：
3.1
作者：
Chen, Kai;Cai, Weibo;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
[18F] FBEM的自动放射化合物合成：用于肽和蛋白质放射性氟化的硫醇反应性合成。
影响因子：
1.6
作者：
Kiesewetter, Dale O.;Jacobson, Orit;Lang, Lixin;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan