1 Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
2 Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK; Imanova Centre for Imaging Sciences, London, UK.
J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.
Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume ( V) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake ( V) as 1.40 mL · cm, which generated a specific-to-nondisplaceable ratio ( BP) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. V increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, V did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.
转位蛋白 18kDa(TSPO)已被广泛用作几种放射性配体(包括[C]PBR28)的神经炎症标志物进行成像。为了研究年龄、性别和肥胖对 TSPO 结合的影响,并确定是否可以使用更少的放射性高效液相色谱(radio-HPLC)测量动脉血样来准确评估这种结合,我们创建了一个包含 48 名健康受试者的数据库,这些受试者接受了[C]PBR28 扫描(23 名高亲和力结合者(HAB)和 25 名混合亲和力结合者(MAB),20 名女性/28 名男性,年龄:40.6±16.8 岁)。使用 23 个代谢物校正的动脉样本进行 Logan 图分析后,发现 HAB 组所有脑区的总分布容积(V)均高出 1.2 倍。此外,多态性图估计不可置换摄取量(V)为 1.40ml·cm,这在 HAB 中产生了 1.6±0.6 的特异性-不可置换比(BP),在 MAB 中为 1.1±0.6。V 在几乎所有区域都随年龄显著增加,并且可以通过 6 个动脉样本的 radio-HPLC 测量得到很好的估计。然而,V 与体重指数不相关,不受性别影响。这些结果强调了在[C]PBR28 研究中应考虑哪些患者特征,并提出了更轻松地进行此类研究并使用更少血样的方法。