用于体内监测腺病毒介导基因治疗的FES-hERL正电子发射断层显像示踪剂-报告基因系统的基础评估
Basic evaluation of FES-hERL PET tracer-reporter gene system for in vivo monitoring of adenoviral-mediated gene therapy.
作者信息
Lohith Talakad Goolaiah, Furukawa Takako, Mori Tetsuya, Kobayashi Masato, Fujibayashi Yasuhisa
机构信息
Biomedical Imaging Research Center, University of Fukui, 23-3, Matsuoka- Shimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan.
出版信息
Mol Imaging Biol. 2008 Sep;10(5):245-52. doi: 10.1007/s11307-008-0149-0. Epub 2008 Jun 12.
PURPOSE
The purpose of the study is to evaluate the feasibility of human estrogen receptor alpha ligand binding domain (hERL) as a reporter gene in combination with positron emission tomography (PET) probe, 16alpha-[18F]fluoro-17beta-estradiol (FES), in an adenovirus gene delivery system.
METHODS
An adenoviral vector (test), carrying hERL gene and a model angiogenesis therapeutic gene (human thymidine phosphorylase, hTP) was constructed along with a control vector. In vitro radioligand binding and expression studies were performed on various cell lines. The control and test viruses were injected into contralateral adductor muscles of a rat followed by FES-PET imaging and immunohistochemical staining of resected muscle samples.
RESULTS
A high FES uptake accompanied by hERL and hTP expression was obtained both in vitro and in vivo by the test adenovirus infection.
CONCLUSION
Considering the versatile tissue permeability of the probe, highly efficient gene expression, and safeness for human use, we expect our reporter gene system to have favorable characteristics for clinical application.
目的
本研究旨在评估在腺病毒基因递送系统中，人雌激素受体α配体结合域（hERL）作为报告基因与正电子发射断层扫描（PET）探针16α-[18F]氟-17β-雌二醇（FES）联合使用的可行性。
方法
构建携带hERL基因和模型血管生成治疗基因（人胸苷磷酸化酶，hTP）的腺病毒载体（测试载体）以及对照载体。对多种细胞系进行体外放射性配体结合和表达研究。将对照病毒和测试病毒注射到大鼠的对侧内收肌中，随后进行FES-PET成像以及对切除的肌肉样本进行免疫组织化学染色。
结果
通过测试腺病毒感染，在体外和体内均获得了高FES摄取，并伴有hERL和hTP表达。
结论
考虑到探针具有广泛的组织渗透性、高效的基因表达以及对人体使用的安全性，我们期望我们的报告基因系统具有良好的临床应用特性。
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