PDF(Pubmed)
Abstract：
Positron emission tomography (PET) imaging employs positron-emitting radioisotopes to visualize biological processes in living subjects with high sensitivity and quantitative accuracy. As the most translational molecular imaging modality, PET can detect and image a wide range of radiotracers with minimal or no modification to parent drugs or targeting molecules. This Perspective provides a comprehensive analysis of developing PET radioligands using allosteric modulators for the metabotropic glutamate receptor subtype 4 (mGluR4) as a therapeutic target for neurological disorders. We focus on the selection of lead compounds from various chemotypes of mGluR4 positive allosteric modulators (PAMs) and discuss the challenges and systematic characterization required in developing brain-penetrant PET tracers specific for mGluR4. Through this analysis, we offer insights into the development and evaluation of PET ligands. Our review concludes that further research and development in this field hold great promise for discovering effective treatments for neurological disorders.
摘要：
正电子发射断层扫描（PET）成像采用正电子发射放射性同位素，以高灵敏度和定量精度可视化活体受试者的生物过程。作为最平移的分子成像模式，PET可以检测和成像广泛的放射性示踪剂，而对母体药物或靶向分子的修饰最小或没有修饰。该观点提供了使用代谢型谷氨酸受体亚型4（mGluR4）的变构调节剂作为神经系统疾病的治疗靶标来开发PET放射性配体的综合分析。我们专注于从mGluR4正变构调节剂（PAMs）的各种化学型中选择先导化合物，并讨论了开发针对mGluR4的脑穿透性PET示踪剂所需的挑战和系统表征。通过这种分析,我们提供有关PET配体的开发和评估的见解。我们的评论得出结论，该领域的进一步研究和开发对于发现神经系统疾病的有效治疗方法具有很大的希望。
