Development of PET probes targeting P2X7 receptor for imaging neuroinflammation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09904
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: SHUKURI Miho 昭和薬科大学, 薬学部, 助教 (20525571)
• Co-Investigator(Kenkyū-buntansha): 加藤 孝一 国立研究開発法人国立精神・神経医療研究センター, 脳病態統合イメージングセンター, 室長 (50382198)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: PET / ミクログリア / P2X7受容体

Outline of Final Research Achievements

The aim of the present study was the development of PET probes targeting P2X7 purinoreceptor (P2X7R) for imaging neuroinflammation.
In this study, we synthesized 11C labeled pyroglutamic acid amide derivatives (11C-PGAAs) and performed PET studies by using rats treated with intrastriatal injection of lipopolysacchalaide (LPS). The increased radioactivities of 11C-PGAAs were shown in the LPS treated hemisphere. Kinetic analysis of PET data revealed that the uptake values of 11C-PGAAs in the brain were not so high. In immunohistochemical studies, we found the activated microglia expressing increment of P2X7R in the brain regions where 11C-PGAAs showed high radioactivity. These results suggest the possibility of P2X7R as an imaging target specific to activated microglia during neuroinflammatory processes.
Although further studies to improve brain uptake are required, 11C-PGAAs showed some adequate properties for imaging P2X7R in neuroinflammation with PET.

Free Research Field

放射薬品学