Radionuclide reporter gene imaging for cardiac gene therapy
Radionuclide reporter gene imaging for cardiac gene therapy
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DOI：
10.1007/s00259-007-0438-x
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发表时间：
2007-06-01
影响因子：
9.1
通讯作者：
Tamaki, Nagara
中科院分区：
文献类型：
--
作者：
Inubushi, Masayuki;Tamaki, Nagara
在心脏基因治疗领域，血管生成基因治疗已被最广泛的研究。1998年报道了第一个心脏血管生成基因治疗的临床试验，高峰期有20多个临床试验方案正在评估中。然而，由于缺乏治疗效果和病毒载体潜在风险的决定性证据，大多数试验已经停止。为了进一步推进心脏血管生成基因治疗，需要解决剩余的开放问题：需要改进基因转移方法，调节基因表达，开发更安全的载体和优化治疗基因。出于这些目的，活生物体中基因表达的成像非常重要。在放射性核素报告基因成像中，转移到细胞核中的“报告基因”编码保留正电子或单光子发射体的互补“报告探针”的蛋白质;因此，报告基因的表达可以用正电子发射断层扫描或单光子发射计算机断层扫描成像。因此，在基因治疗的情况下，可以非侵入性地监测治疗基因与报道基因共表达的位置、幅度和持续时间。在不久的将来，基因治疗可能会发展为与干/祖细胞移植联合治疗，即所谓的基于细胞的基因治疗或基因修饰的细胞治疗。结论放射性核素报告基因显像有望为这种新的治疗方法的有效性提供证据。以及研究新血管形成的分子机制和与常规基因治疗的进一步进展相关的安全性问题，疗法
Introduction In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, "reporter genes" transferred into cell nuclei encode for a protein that retains a complementary "reporter probe" of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy.Conclusion Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy.