Development of PET probes of neuroprotective molecular components in oriental medicines

2015 Fiscal Year Final Research Report

• Project/Area Number: 25242070
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: SUZUKI Masaaki 国立研究開発法人国立長寿医療研究センター, 能機能画像診断開発部, 特任研究員 (90093046)
• Co-Investigator(Kenkyū-buntansha): ISHII Hideki 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (80425610) ; DOI Hisashi 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (00421818) ; KOYAMA Hiroko 岐阜大学, 大学院医学系研究科, 助教 (50402160)
• Co-Investigator(Renkei-kenkyūsha): UMEMURA Kazuo 浜松医科大学, 医学部, 教授 (40232912)
• Research Collaborator: OGATA Aya
• Project Period (FY): 2013-10-21 – 2016-03-31
• Keywords: 11C標識 / PET分子イメージング / ギンゴライド＆ジンセノサイド / 脳移行性 / 糖輸送体

Outline of Final Research Achievements

The ginkgolide is the most attractive components of the ginkgo biloba extracts, possessing neuroprotective effects. It has been reported that ginkgolide B (GB) shows almost no brain permeability as judged by PET molecular imaging. Here, we have found that the GB benzyl derivative with enhanced hydrophobicity shows higher binding affinity for PAF receptor than GB and that the corresponding 11C-labeled methylbenzyl GB exhibits monkey-brain permeability to some extent and high brain uptake for the rat after pre-administration of P-glycoprotein inhibitor. Moreover, in expectation of further higher uptake of GB into the brain, we have synthesized a new prodrug linked with glucose as a substrate for a glucose transporter expressed in the blood-brain barrier. In addition, we have established the synthesis of boron and stannyl precursors of dipterocarpol submitted for our-devised rapid C-[11C]methylation, eventually with an aim to synthesize a 11C-labeled ginsenoside.

Free Research Field

生体分子科学・生物分子化学