Walker Matthew D, Dinelle Katherine, Kornelsen Rick, Lee Nathan V, Miao Qing, Adam Mike, Takhar Christine, Mak Edwin, Schulzer Michael, Farrer Matthew J, Sossi Vesna
Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
J Cereb Blood Flow Metab. 2015 Aug;35(8):1331-8. doi: 10.1038/jcbfm.2015.54. Epub 2015 Apr 1.
Neuroinflammation in the aging rat brain was investigated using [(11)C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson's disease in humans. Seventy [(11)C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of VT. In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas VT increased by 91% from 30 to 57 mL/cm(3). Standard uptake value and VT were strongly correlated (r = 0.52, 95% confidence interval (CI) = 0.31 to 0.69, n = 37). The plasma free fraction, fp, was 0.21 ± 0.03 (mean ± standard deviation, n = 53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than VT; coefficients of variation were 13% (n = 27) and 29% (n = 12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for VT. These data show that [(11)C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain.
利用[¹¹C]PBR28微型正电子发射断层扫描（microPET）成像技术对老年大鼠脑内的神经炎症进行了研究。将正常大鼠与携带LRRK2 p.G2019S突变的转基因大鼠一起进行研究；这种突变会增加人类患帕金森病的风险。共采集了70次[¹¹C]PBR28正电子发射断层扫描（PET）图像。通过动脉采血实现示踪剂动力学建模和VT的估计。还进行了体外放射自显影。PBR28摄取量随年龄增长而增加，非转基因大鼠和转基因大鼠之间无差异。在12个月的衰老过程中（4至16个月），标准摄取值（SUV）从0.44 g/mL增加到0.69 g/mL，增幅为56%，而VT从30 mL/cm³增加到57 mL/cm³，增幅为91%。标准摄取值与VT高度相关（r = 0.52，95%置信区间（CI）= 0.31至0.69，n = 37）。血浆游离分数fp为0.21±0.03（平均值±标准差，n = 53）。在16个月的衰老过程中（4至20个月），体外结合增加了19%。SUV在不同大鼠之间的变异性小于VT；变异系数分别为13%（n = 27）和29%（n = 12）。SUV的组内相关系数为0.53，但VT的组内相关系数实际上为零。这些数据表明，[¹¹C]PBR28在脑内的摄取量随年龄增长而增加，这意味着老年大脑中微胶质细胞的激活增加。
