BHF-University of Edinburgh Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.
J Cereb Blood Flow Metab. 2024 Mar;44(3):397-406. doi: 10.1177/0271678X231205661. Epub 2023 Oct 5.
Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [F]LW223, in mice and specifically assess its volume of non-displaceable binding () in brain as well as investigate the use of simplified analysis approaches for quantification of [F]LW223 PET data. Adult male mice were injected with [F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate of [F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values () and apparent volume of distribution (), were investigated. [F]LW223 had low in the brain (<10% of total binding) and low radiometabolism (∼15-20%). The 2-tissue compartment model provided the best fit for [F]LW223 PET data, although its correlation with or allowed for [F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [F]LW223 has the required properties to become a successful TSPO PET radiotracer.
神经炎症与许多脑部疾病有关，是脑病理学的常见特征。在正电子发射断层扫描（PET）研究中，最著名的神经炎症生物标志物之一是 18 kDa 转位蛋白（TSPO）。本研究旨在研究新型 TSPO PET 示踪剂[F]LW223 在小鼠中的结合动力学，并特别评估其在大脑中的非置换结合容积（），以及研究简化分析方法在[F]LW223 PET 数据定量中的应用。成年雄性小鼠注射[F]LW223 和不同浓度的 LW223（0.003-0.55mg/kg），以估计[F]LW223的。进行了带有动脉输入函数研究和放射性代谢产物研究的动态 PET 成像。研究了简化的定量方法，标准摄取值（）和表观分布容积（）。[F]LW223 在大脑中的结合率较低（<总结合的 10%），放射性代谢率较低（约 15-20%）。2 组织隔室模型为[F]LW223 PET 数据提供了最佳拟合，尽管其与或的相关性允许在使用更简单的实验和分析方法时，对健康动物的[F]LW223 脑 PET 数据进行定量。[F]LW223 具有成为成功的 TSPO PET 示踪剂的所需特性。
