The positron emission tomography (PET) radiotracer [¹¹C]PBR28 has been increasingly used to image the translocator protein (TSPO) as a marker of neuroinflammation in a variety of brain disorders. Interrelatedly, similar clinical populations can also exhibit altered brain perfusion, as has been shown using arterial spin labelling in magnetic resonance imaging (MRI) studies. Hence, an unsolved debate has revolved around whether changes in perfusion could alter delivery, uptake, or washout of the radiotracer [¹¹C]PBR28, and thereby influence outcome measures that affect interpretation of TSPO upregulation. In this simultaneous PET/MRI study, we demonstrate that [¹¹C]PBR28 signal elevations in chronic low back pain patients are not accompanied, in the same regions, by increases in cerebral blood flow (CBF) compared to healthy controls, and that areas of marginal hypoperfusion are not accompanied by decreases in [¹¹C]PBR28 signal. In non-human primates, we show that hypercapnia-induced increases in CBF during radiotracer delivery or washout do not alter [¹¹C]PBR28 outcome measures. The combined results from two methodologically distinct experiments provide support from human data and direct experimental evidence from non-human primates that changes in CBF do not influence outcome measures reported by [¹¹C]PBR28 PET imaging studies and corresponding interpretations of the biological meaning of TSPO upregulation.

正电子发射断层扫描 (PET) 放射性示踪剂 [ ¹¹ C]PBR28 已越来越多地用于对转运蛋白 (TSPO) 进行成像，作为各种脑部疾病中神经炎症的标志物。相关地，类似的临床人群也可以表现出改变的脑灌注，正如在磁共振成像 (MRI) 研究中使用动脉自旋标记所显示的那样。因此，尚未解决的争论围绕着灌注变化是否会改变放射性示踪剂 [ ¹¹ C]PBR28 的递送、摄取或清除，从而影响影响 TSPO 上调解释的结果测量。在这项同时进行的 PET/MRI 研究中，我们证明 [ ¹¹C] 与健康对照组相比，在相同区域，慢性腰痛患者的 PBR28 信号升高不伴随脑血流量 (CBF) 的增加，并且边缘低灌注区域不伴随 [ ¹¹ C]的降低PBR28 信号。在非人类灵长类动物中，我们表明在放射性示踪剂输送或冲洗期间高碳酸血症引起的 CBF 增加不会改变 [ ¹¹ C]PBR28 结果测量。两个方法学上不同的实验的综合结果提供了来自人类数据和来自非人类灵长类动物的直接实验证据的支持，即 CBF 的变化不会影响 [ ¹¹ C]PBR28 PET 成像研究报告的结果测量以及对 TSPO 生物学意义的相应解释上调。