Haberkorn Uwe, Altmann Annette, Mier Walter, Eisenhut Michael
Department of Nuclear Medicine, University of Heidelberg, Germany.
Semin Nucl Med. 2004 Jan;34(1):4-22. doi: 10.1053/j.semnuclmed.2003.09.003.
The assessment of gene function following the completion of human genome sequencing may be performed using radionuclide imaging procedures. These procedures are needed for the evaluation of genetically manipulated animals or newly designed biomolecules, which requires a thorough understanding of physiology, biochemistry, and pharmacology. The experimental approaches will involve many new technologies, including in vivo imaging with single photon emission computed tomography and positron emission tomography. Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers, or using in vivo reporter genes, such as genes encoding enzymes, receptors, antigens, or transporters. Visualization of in vivo reporter gene expression can be performed using radiolabeled substrates, antibodies, or ligands. Combinations of specific promoters and in vivo reporter genes may deliver information about the regulation of the corresponding genes. Furthermore, protein-protein interactions and activation of signal transduction pathways may be visualized noninvasively. The role of radiolabeled antisense molecules for the analysis of messenger ribonucleic acid (RNA) content has to be investigated. However, possible applications are therapeutic intervention using triplex oligonucleotides with therapeutic isotopes, which can be brought near to specific deoxyribonucleic acid sequences to induce deoxyribonucleic acid strand breaks at selected loci. Imaging of labeled siRNA makes sense if these are used for therapeutic purposes to assess the delivery of these new drugs to their target tissue. Pharmacogenomics will identify new surrogate markers for therapy monitoring, which may represent potential new tracers for imaging. Drug distribution studies for new therapeutic biomolecules are needed at least during preclinical stages of drug development. New treatment modalities, such as gene therapy with suicide genes, will need procedures for therapy planning and monitoring. Finally, new biomolecules will be developed by bioengineering methods, which may be used for the isotope-based diagnosis and treatment of disease.
人类基因组测序完成后,可使用放射性核素成像程序对基因功能进行评估。这些程序对于评估基因操作动物或新设计的生物分子是必要的,这需要对生理学、生物化学和药理学有透彻的了解。实验方法将涉及许多新技术,包括单光子发射计算机断层扫描和正电子发射断层扫描的体内成像。核医学程序可用于使用已有的和新的示踪剂,或使用体内报告基因,如编码酶、受体、抗原或转运蛋白的基因,来确定基因功能和调控。体内报告基因表达的可视化可使用放射性标记的底物、抗体或配体来进行。特定启动子和体内报告基因的组合可提供有关相应基因调控的信息。此外,蛋白质-蛋白质相互作用和信号转导途径的激活可通过非侵入性方式进行可视化。放射性标记的反义分子在信使核糖核酸(RNA)含量分析中的作用有待研究。然而,可能的应用是使用带有治疗性同位素的三链寡核苷酸进行治疗干预,这些寡核苷酸可接近特定的脱氧核糖核酸序列,以在选定位点诱导脱氧核糖核酸链断裂。如果标记的小干扰RNA(siRNA)用于治疗目的以评估这些新药向其靶组织的递送,那么对其进行成像就有意义。药物基因组学将识别用于治疗监测的新替代标志物,这些标志物可能代表潜在的新成像示踪剂。至少在药物开发的临床前阶段,需要对新的治疗性生物分子进行药物分布研究。新的治疗方式,如用自杀基因进行基因治疗,将需要治疗计划和监测程序。最后,将通过生物工程方法开发新的生物分子,这些生物分子可用于基于同位素的疾病诊断和治疗。