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TSPO Versus P2X7 as a Target for Neuroinflammation: An In Vitro and In Vivo Study
The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2020-04-01 , DOI: 10.2967/jnumed.119.231985
Donatienne Van Weehaeghe , Evelien Van Schoor , Joke De Vocht , Michel Koole , Bala Attili , Sofie Celen , Lieven Declercq , Dietmar R. Thal , Philip Van Damme , Guy Bormans , Koen Van Laere

Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare 18F-DPA714, a second-generation translocator protein tracer, with 11C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with 18F-DPA714 and 11C-JNJ717 was performed on human ALS brain sections in comparison to immunofluorescence with Iba1 and GFAP. For the in vivo portion, 3 male patients with early-stage ALS (59.3 ± 7.2 y old) and 6 healthy volunteers (48.2 ± 16.5 y old, 2 men and 4 women) underwent dynamic PET/MR scanning with 18F-DPA714 and 11C-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in 11C-JNJ717 binding but did show increased 18F-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in 18F-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, 18F-DPA714 showed increased signal whereas 11C-JNJ717 was not elevated.



中文翻译:

TSPO与P2X7作为神经炎症的靶标:一项体内和体外研究

神经炎症在肌萎缩性侧索硬化症(ALS)中很重要。P2X7受体(P2X7R)是神经发炎的有希望的目标。这项研究的目的是比较ALS体内和体外的第二代转运蛋白示踪剂18 F-DPA714与新型P2X7R示踪剂11 C-JNJ717。方法:对于研究的体外部分,与使用Iba1和GFAP进行免疫荧光分析相比,在人ALS脑部进行了18 F-DPA714和11 C-JNJ717放射自显影。对于体内部分,3例早期ALS(59.3±7.2岁)的男性患者和6例健康志愿者(48.2±16.5 y岁,2例男性和4例女性)进行了动态PET / MR扫描,18例F-DPA714和11 C-JNJ717。使用洛根图计算分布图像,并在关注体积的基础上进行分析。结果:放射自显影显示11 C-JNJ717结合无差异,但确实显示了运动皮层中与Iba1表达相关的18 F-DPA714结合增加(胶质细胞)。在体内观察到类似的发现,运动皮层中18 F-DPA714的结合增加了13%。结论:在有症状的ALS患者中,18 F-DPA714显示信号增加,而11 C-JNJ717没有升高。

更新日期:2020-04-23
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