Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Nucl Med Biol. 2010 Jan;37(1):9-15. doi: 10.1016/j.nucmedbio.2009.09.002. Epub 2009 Oct 22.
Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [(11)C]-PK11195 can be used to study neuroinflammation in these disorders. However, [(11)C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [(11)C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis.
Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [(11)C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake.
In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [(11)C]-DAA1106 was found in almost all examined brain areas (24-71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [(11)C]-DAA1106 uptake in HSE rats (54-84%; P<.001). The plasma and brain time-activity curves showed rapid uptake of [(11)C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to a two-tissue compartment model.
[(11)C]-DAA1106 showed a high and specific ex vivo uptake in the encephalitic rat brain. However, neuroinflammation could not be demonstrated in vivo by [(11)C]-DAA1106 PET. Quantification of the uptake of [(11)C]-DAA1106 using plasma sampling is not optimal, due to rapid tissue uptake, slow tissue clearance and low plasma activity.
许多神经和精神疾病都与神经炎症有关。正电子发射断层扫描（PET）与 [(11)C]-PK11195 可用于研究这些疾病中的神经炎症。然而，[(11)C]-PK11195 可能不够敏感，无法观察到轻度神经炎症。[(11)C]-N-(2,5-二甲氧基苄基)-N-(4-氟-2-苯氧基苯基）-乙酰胺（DAA1106）作为一种潜在更敏感的神经炎症 PET 示踪剂，在单纯疱疹脑炎大鼠模型中进行了评估。
雄性 Wistar 大鼠经鼻腔接种 HSV-1（HSE）或磷酸盐缓冲盐水（对照）。接种后第 6 或第 7 天，进行小动物 [(11)C]-DAA1106 PET 扫描，随后进行离体生物分布。进行动脉采血以定量摄取。
在 HSE 大鼠中，与对照组相比，几乎所有检查的脑区的 [(11)C]-DAA1106 离体摄取均显著升高（24-71%，P<.05），但在体内摄取没有差异。用未标记的 PK11195 预处理可有效降低 HSE 大鼠的 [(11)C]-DAA1106 摄取（54-84%；P<.001）。血浆和脑时间-活性曲线显示 [(11)C]-DAA1106 迅速摄取到组织中。数据与 Logan 分析拟合良好，但不能拟合双组织室模型。
[(11)C]-DAA1106 在脑炎大鼠脑中显示出高特异性的体外摄取。然而，[(11)C]-DAA1106 PET 无法在体内显示神经炎症。由于组织摄取迅速、组织清除缓慢和血浆活性低，使用血浆采样定量 [(11)C]-DAA1106 的摄取不是最佳方法。
