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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography
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Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography

机译：用正电子发射断层显像技术对活体动物中腺病毒指导的报告基因表达进行成像

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摘要

We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using Positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluorogan -ciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron- emitting FGCV as a PET reporter probe, we imaged adellovirus-directed hepatic expression of the HSVl-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression ofr2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23 for ganciclovir and 0-3 for FGCV. Repeated, noninvasive, and quantitativc imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.
机译：我们正在开发定量测定法，以使用正电子发射断层扫描（PET）在动物中反复和无创地对报告基因的表达进行成像。我们合成了发射正电子的8- [18F] fluorogan -ciclovir（FGCV），并证明该化合物是单纯疱疹病毒1胸苷激酶（HSV1-TK）的底物。使用发射正电子的FGCV作为PET报告探针，我们在活小鼠中成像了Adellovirus定向的HSV1-tk报告基因的肝表达。每克肝脏保留的FGCV注射剂量百分比与肝HSV1-tk报告基因表达水平r2> 0.80之间存在显着正相关。在体内HSV1-tk表达的相似范围内，更昔洛韦每克肝脏保留的注射剂量百分比为0-23，对于FGCV为0-3。重复，无创和定量成像的PET报告基因表达应该是研究人类基因治疗，器官/细胞移植以及转基因小鼠中基因表达的环境和行为调节的有价值的工具。

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