Janssen Bieneke, Vugts Danielle J, Funke Uta, Spaans Arnold, Schuit Robert C, Kooijman Esther, Rongen Marissa, Perk Lars R, Lammertsma Adriaan A, Windhorst Albert D
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
J Labelled Comp Radiopharm. 2014 Jun 30;57(8):509-16. doi: 10.1002/jlcr.3206. Epub 2014 Jul 3.
Neuroinflammation, in particular activation of microglia, is thought to play an important role in the progression of neurodegenerative diseases. In activated microglia, the purinergic P2X7 receptor is upregulated. A-740003, a highly affine and selective P2X7 receptor antagonist, is a promising candidate for the development of a radiotracer for imaging of neuroinflammation by positron emission tomography. For this purpose, [(11)C]A-740003 was synthesised and evaluated in vivo with respect to both tracer metabolism and biodistribution. In plasma, a moderate metabolic rate was seen. In healthy rat brain, only marginal uptake of [(11)C]A-740003 was observed and, therefore, metabolites in brain could not be determined. Whether the minimal brain uptake is due to the low expression levels of the P2X7 receptor in healthy brain or to limited transport across the blood-brain barrier has yet to be elucidated.
神经炎症，尤其是小胶质细胞的激活，被认为在神经退行性疾病的进展中起重要作用。在激活的小胶质细胞中，嘌呤能P2X7受体上调。A-740003是一种高亲和力和选择性的P2X7受体拮抗剂，是通过正电子发射断层扫描成像神经炎症的放射性示踪剂开发的有前景的候选物。为此，合成了[(11)C]A-740003并在体内对示踪剂代谢和生物分布进行了评估。在血浆中，观察到中等代谢率。在健康大鼠脑中，仅观察到[(11)C]A-740003的微量摄取，因此，无法确定脑中的代谢物。脑中的微量摄取是由于健康脑中P2X7受体的低表达水平还是由于穿过血脑屏障的转运受限，还有待阐明。
