Toyohara Jun
Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo1730015, Japan.
Curr Pharm Des. 2016;22(38):5830-5836. doi: 10.2174/1381612822666160804092258.
Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a functional blood-brain barrier (BBB). P-gp pumps out multiple types of molecules from the brain parenchyma into the blood. Therefore, altered P-gp function at the BBB will change the concentrations of therapeutic drugs in the central nervous system (CNS) and hence impact the toxicity and efficacy of CNS drugs. Positron emission tomography (PET) is the only way to non-invasively measure P-gp function in the living human brain. PET imaging of P-gp function was first demonstrated in 1998 with the substrate tracer racemic [11C]verapamil. Since then, several drug interaction studies and proof-of-concept studies regarding drug resistance have been performed with P-gp PET imaging. Although preclinical findings have been very positive regarding the possibilities and importance of P-gp PET imaging, very few studies have shown the clinical relevance of P-gp PET imaging in different disorders of the brain. This review summarizes the pharmacological studies with PET using substrate tracers and emphasizes the importance of PET imaging to understand the mechanism of action of CNS drugs.
脑内的毛细血管内皮细胞表达P-糖蛋白（P-gp），它作为功能性血脑屏障（BBB）发挥作用。P-gp将多种类型的分子从脑实质泵入血液。因此，血脑屏障处P-gp功能的改变会改变中枢神经系统（CNS）中治疗药物的浓度，进而影响CNS药物的毒性和疗效。正电子发射断层扫描（PET）是在活体人脑中无创测量P-gp功能的唯一方法。1998年首次用底物示踪剂外消旋[11C]维拉帕米进行了P-gp功能的PET成像。从那时起，已经用P-gp PET成像进行了几项关于药物相互作用的研究和耐药性的概念验证研究。尽管临床前研究对于P-gp PET成像的可能性和重要性给出了非常积极的结果，但很少有研究显示P-gp PET成像在不同脑部疾病中的临床相关性。这篇综述总结了使用底物示踪剂进行PET的药理学研究，并强调了PET成像对于理解CNS药物作用机制的重要性。
