School of Chemistry, Faculty of Science, The University of Sydney, New South Wales, Australia.
School of Chemistry, Faculty of Science, The University of Sydney, New South Wales, Australia.
Semin Nucl Med. 2024 Nov;54(6):856-874. doi: 10.1053/j.semnuclmed.2024.09.007. Epub 2024 Oct 29.
The translocator protein (TSPO) is a biomarker for imaging neuroinflammation via Positron Emission Tomography (PET) across a broad range of CNS conditions. Most clinically used PET ligands targeting TSPO have limitations, including high lipophilicity and off-target binding or poor binding to a mutated TSPO isoform present in up to 30% of the population. Research efforts over the past decade have focused on development of improved TSPO PET radiotracers that overcome these limitations. This review provides a critical analysis of the development and validation of these so-called "third-generation" radiotracers in clinical and preclinical settings. We also offer our perspective on the future directions of TSPO PET imaging, including recommendations for overcoming current challenges and capitalizing on emerging opportunities in molecular imaging for neuroinflammatory diseases.
转位蛋白（TSPO）是通过正电子发射断层扫描（PET）对广泛的中枢神经系统疾病进行神经炎症成像的生物标志物。大多数用于靶向 TSPO 的临床 PET 配体都存在局限性，包括高亲脂性、非靶点结合或与高达 30%人群中存在的突变型 TSPO 同工型结合不良。过去十年的研究重点是开发克服这些限制的改进型 TSPO PET 放射性示踪剂。本综述对这些所谓的“第三代”放射性示踪剂在临床和临床前环境中的开发和验证进行了批判性分析。我们还对 TSPO PET 成像的未来方向提出了看法，包括克服当前挑战和利用神经炎症性疾病分子成像中新兴机会的建议。
