Imagerie Moléculaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France.
Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, 8091 Zurich, Switzerland.
Pharmacol Ther. 2018 Sep;189:104-122. doi: 10.1016/j.pharmthera.2018.04.006. Epub 2018 Apr 22.
Transporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imaging allows pharmacokinetic parameters in different tissues and organs to be obtained in a non-invasive or minimally invasive way. The aim of this overview is to summarize the current status in the field of molecular imaging of drug transporters. The overview is focused on human studies, both for the characterization of transport systems for imaging agents as well as for the determination of drug pharmacokinetics, and makes reference to animal studies where necessary. We conclude that despite certain methodological limitations, imaging has a great potential to study transporters at work in humans and that imaging will become an important tool, not only in drug development but also in medicine. Imaging allows the mechanistic aspects of transport proteins to be studied, as well as elucidating the influence of genetic background, pathophysiological states and drug-drug interactions on the function of transporters involved in the disposition of drugs.
参与药物和溶质跨生物膜渗透的转运系统被认为是药代动力学的关键决定因素。通常，从活体生物组织中推断出膜转运体对药物暴露的作用需要进行侵入性操作，而这些操作在人体上无法进行。近年来，成像方法在仪器、新型成像探针的合成以及数据分析工具方面取得了重大进展。成像可以非侵入性或微创的方式获得不同组织和器官中的药代动力学参数。本文综述的目的是总结药物转运体分子成像领域的现状。本文综述重点关注人类研究，包括用于成像剂转运系统的表征以及药物药代动力学的确定，并在必要时参考动物研究。我们的结论是，尽管存在某些方法学限制，但成像在研究人类转运体的工作方面具有很大的潜力，并且成像将成为一种重要的工具，不仅在药物开发中，而且在医学中也是如此。成像可以研究转运蛋白的机制方面，以及阐明遗传背景、病理生理状态和药物相互作用对参与药物处置的转运体功能的影响。
