Development of DNA aptamer PET ligands targeting toll-like receptor 4

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17187
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Gihu University of Medical Science (2020-2021); National Center for Geriatrics and Gerontology (2019)
• Principal Investigator: OGATA Aya 岐阜医療科学大学, 薬学部, 助教 (10805857)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: PET / TLR4 / 短寿命放射性核種

Outline of Final Research Achievements

The purpose of this study is to develop a PET imaging ligand that visualizes TLR4 minimally invasively as a factor involved in neuroinflammation in various neurodegenerative diseases.In this study, we evaluated the brain permeability and nuclease resistance of DNA aptamers targeting TLR4 using fluorescently labeled DNA aptamers. As a result, it was shown that the DNA aptamer has a good brain permeability and nuclease resistance. In parallel, rat brain sections of the same strain as the rats undergoing PET imaging were immunostained. It was suggested that TLR4 is expressed not only in microglia and astrocytes but also in nerve cells. In addition, since the synthesis of precursors of 18F and 11C labeled substances has been completed, labeling will be carried out in the future.

Free Research Field

放射線科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、様々な神経変性疾患における神経炎症に関わる因子として、TLR4を低侵襲的に可視化するPETイメージングリガンドを開発研究を実施した。TLR4は脳内では主にグリア細胞膜表面に発現し、LPSなどが結合することで活性化・炎症性サイトカインを産生し、炎症反応を惹起する。アルツハイマー病患者の脳内においてもTLR4の発現量は増えている。TLR4を標的とするPETリガンドを開発し、TLR4の脳内密度や分布などの情報が得られるバイオマーカーとなりえれば、神経変性疾患における治療法の開発に役立つことが期待される。