新型TSPO分子探针18F-VUIIS1008探测活化小胶质细胞在炎性反应中的作用

Effect of a novel TSPO-targeted molecular probe 18F-VUIIS1008 in activated microglia cells of the inflammatory response

目的:探讨外周型苯二氮[艹卓]受体转运蛋白(TSPO)的分子探针18F-VUIIS1008在不同条件下β淀粉样蛋白(Aβ)活化BV-2小胶质细胞的药代动力学特征及不同浓度地塞米松抑制后的药代动力学变化。方法:用小鼠的小胶质细胞BV-2细胞进行体外细胞摄取实验。不同浓度Aβ活化,在不同时间点测定BV-2细胞对18F-VUIIS1008的摄取率;在不同浓度地塞米松干预下,测定不同时间点BV-2细胞对18F-VUIIS1008的摄取率。结果:随着Aβ干预时间的延长和浓度的增加,BV-2细胞对18F-VUIIS1008摄取逐渐增加,12 h达到高峰,24 h略有下降。随着18F-VUIIS1008作用时间延长,BV-2细胞对18F-VUIIS1008摄取逐渐升高,60 min时达到最大摄取比值,90 min略有下降。其中在10.0μg/ml的Aβ活化12 h后加入18F-VUIIS1008作用60 min后Cin/Cout放射性比值最高,为2.08±0.40。在不同浓度的抗炎药物(地塞米松)作用下,随着时间的延长及地塞米松的浓度增加,Cin/Cout放射性比值逐渐减低。在100μmol/L地塞米松抑制下,BV-2小胶质细胞90 min对18F-VUIIS1008的摄取最低,为0.15±0.12。结论:Aβ可活化BV-2小胶质细胞,经典抗炎药物(地塞米松)可抑制小胶质细胞的活化。18F-VUIIS1008可能作为TSPO的分子探针,动态监测小胶质细胞的活化状态。

Objective To investigate the pharmacokinetics of uptaked the novel TSPO radiotracer 18F-VUIIS1008 by β amyloid protein(Aβ) activates BV-2 microglia cells under different conditions and after inhibition with different concertrations of dexamethasone in vitro cells.Method In vitro cellular uptake assay was performed on BV-2 microglia cells in mice.The uptake rate of 18F-VUIIS1008 in BV-2 cells was determined at different time poing after the activation of different concentration Aβ and the inhibition of different concentration dexamethasone.Results The uptake rate of 18F-VUIIS1008 increased gradually with the increasing of Aβ intervention time and its concentration.The uptake of the tracer reached the maximum at 12 hours, and then gradually decreased after 24 hours.The uptake increased gradully as the prolonged action time of 18F-VUIIS1008.It reached the peak value at 60 minutes, then it gradually decreased at 90 minutes.The uptake rate of the tracer also showed its maximum value was reached after 12 hours activation of 10.0 μg/ml Aβ and 60 minutes reaction of 18F-VUIIS1008(Cin/Cout was 2.08±0.40).The uptake decreased gradually with the concertration of anti-inflammatory(dexamethasone) increased over time.It also showed that the minimum value was reached after the inhibition of 100 μmol/L dexamethasone for 90 minutes(Cin/Cout was 0.15±0.12).Conclusion Aβ can activate BV-2 microglia cells, and anti-inflammatory drugs(dexamethasone) can inhibit the activation.The study suggests the potential value of 18F-VUIIS1008 being a novel molecular probe targeting TSPO to dynamically monitor the activation state for microglia.