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临床前药物研发中的正电子发射示踪剂。

Positron emitting tracers in pre-clinical drug development.

作者信息

Fernandes E, Barbosa Z, Clemente G, Alves F, Abrunhosa A J

机构信息

ESTeS-C College of Health Technology, Polytechnic Institute of Coimbra, Coimbra, Portugal.

出版信息

Curr Radiopharm. 2012 Apr;5(2):90-8. doi: 10.2174/1874471011205020090.

Abstract

Molecular imaging tools such as Positron Emission Tomography (PET) are increasingly being used in the drug development process. The unrivaled sensitivity of PET coupled with a solid experience in developing highly targeted molecular probes makes this technique a very valuable tool at all stages from pre-clinical development to the clinical phases. Positron emitting tracers allow us to measure, quantitatively, molecular processes and interactions between a candidate drug and its molecular targets. This information can save time and money by directing development towards the most promising compounds and excluding molecules with unfavorable properties that would otherwise only be recognized as failures in latter stages of the process. In this paper we review the application of positron emitting tracers in the pre-clinical stages of the drug development process in the areas of oncology, cardiology, neurosciences and inflammatory diseases. PET tracers provide an important support for drug development in the areas of: discovery of new drug targets, clarification of pathophysiology, identification of potential drug candidates and validation of drug effectiveness, as well as the evaluation of pharmacokinetic and pharmacodynamic parameters in vivo.

摘要

正电子发射断层扫描(PET)等分子成像工具在药物研发过程中的应用越来越广泛。PET无与伦比的灵敏度,再加上在开发高靶向性分子探针方面的丰富经验,使得这项技术在从临床前开发到临床阶段的各个阶段都成为非常有价值的工具。正电子发射示踪剂使我们能够定量测量候选药物与其分子靶点之间的分子过程和相互作用。这些信息可以通过将研发方向指向最有前景的化合物,并排除那些具有不良特性的分子(否则这些分子只会在研发过程的后期才被认定为失败)来节省时间和金钱。在本文中,我们综述了正电子发射示踪剂在肿瘤学、心脏病学、神经科学和炎症性疾病等领域药物研发临床前阶段的应用。PET示踪剂在以下药物研发领域提供了重要支持:发现新的药物靶点、阐明病理生理学、识别潜在的候选药物并验证药物有效性,以及评估体内药代动力学和药效学参数。

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