Inserm U948, Université de Nantes, Nantes Atlantique Universités, EA4274, Institut des Maladies de l'Appareil Digestif, CHU Hôtel Dieu, Nantes, France.
Br J Pharmacol. 2010 Feb;159(4):761-71. doi: 10.1111/j.1476-5381.2009.00412.x. Epub 2009 Oct 8.
Biotherapies involve the utilization of antibodies, genetically modified viruses, bacteria or cells for therapeutic purposes. Molecular imaging has the potential to provide unique information that will guarantee their biosafety in humans and provide a rationale for the future development of new generations of reagents. In this context, non-invasive imaging of gene expression is an attractive prospect, allowing precise, spacio-temporal measurements of gene expression in longitudinal studies involving gene transfer vectors. With the emergence of cell therapies in regenerative medicine, it is also possible to track cells injected into subjects. In this context, the Na/I symporter (NIS) has been used in preclinical studies. Associated with a relevant radiotracer ((123)I(-), (124)I(-), (99m)TcO4(-)), NIS can be used to monitor gene transfer and the spread of selectively replicative viruses in tumours as well as in cells with a therapeutic potential. In addition to its imaging potential, NIS can be used as a therapeutic transgene through its ability to concentrate therapeutic doses of radionuclides in target cells. This dual property has applications in cancer treatment and could also be used to eradicate cells with therapeutic potential in the case of adverse events. Through experience acquired in preclinical studies, we can expect that non-invasive molecular imaging using NIS as a transgene will be pivotal for monitoring in vivo the exact distribution and pharmacodynamics of gene expression in a precise and quantitative way. This review highlights the applications of NIS in biotherapy, with a particular emphasis on image-guided radiotherapy, monitoring of gene and vector biodistribution and trafficking of stem cells.
生物疗法涉及利用抗体、基因修饰病毒、细菌或细胞进行治疗。分子成像有可能提供独特的信息，以保证它们在人类中的生物安全性，并为新一代试剂的未来发展提供依据。在这种情况下，非侵入性的基因表达成像具有很大的吸引力，可以在涉及基因转移载体的纵向研究中，对基因表达进行精确的、时空测量。随着再生医学中细胞疗法的出现，也可以对注入受试者体内的细胞进行跟踪。在这种情况下，钠/碘同向转运体（NIS）已被用于临床前研究。与相关的放射性示踪剂（(123)I(-)、(124)I(-)、(99m)TcO4(-)）结合，NIS 可用于监测基因转移和选择性复制病毒在肿瘤以及具有治疗潜力的细胞中的传播。除了具有成像潜力外，NIS 还可以作为一种治疗性转基因，通过将治疗剂量的放射性核素浓缩在靶细胞中来发挥作用。这种双重特性在癌症治疗中有应用，在发生不良事件时，也可以用于消除具有治疗潜力的细胞。通过在临床前研究中获得的经验，我们可以预期，使用 NIS 作为转基因的非侵入性分子成像将是监测基因表达在体内的确切分布和药效动力学的关键手段，这种方法精确且定量。这篇综述强调了 NIS 在生物治疗中的应用，特别强调了图像引导放疗、基因和载体生物分布监测以及干细胞的运输。
