PDF(Pubmed)
Abstract：
Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by the animal imaging community, mainly because its utility in this area is unproven. We developed a new complementation-based reporter gene system where the large component of split NanoLuc luciferase (LgBiT) presented on the surface of cells (TM-LgBiT) interacts with a radiotracer consisting of the high-affinity complementary HiBiT peptide labeled with a radionuclide. Radiotracer uptake could be imaged in mice using SPECT/CT and bioluminescence within two hours of implanting reporter-gene-expressing cells. Imaging data were validated by ex vivo biodistribution studies. Following the demonstration of complementation between the TM-LgBiT protein and HiBiT radiotracer, we validated the use of the technology in the highly specific in vivo multimodal imaging of cells. These findings highlight the potential of this new approach to facilitate the advancement of cell and gene therapies from bench to clinic.
摘要：
多模态报告基因成像结合敏感性，两个或多个信号的分辨率和平移电位。该方法尚未被动物成像界广泛采用，主要是因为它在这一领域的效用未经证实。我们开发了一种新的基于互补的报告基因系统，其中存在于细胞表面的分裂NanoLuc荧光素酶（LgBiT）的大部分成分（TM-LgBiT）与放射性示踪剂相互作用，该放射性示踪剂由用放射性核素标记的高亲和力互补HiBiT肽组成。在植入报告基因表达细胞的两小时内，可以使用SPECT/CT和生物发光在小鼠中对放射性示踪剂的摄取进行成像。通过离体生物分布研究验证成像数据。在证明TM-LgBiT蛋白和HiBiT放射性示踪剂之间的互补后，我们验证了该技术在高度特异性体内细胞多模态成像中的应用.这些发现强调了这种新方法促进细胞和基因疗法从实验室到临床的发展的潜力。
