Elucidation of mechanisms underlying lifestyle-related diseases and malignant tumors based on in vivo imaging of scavenger receptors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kawashima Hidekazu 京都薬科大学, 薬学部, 准教授 (70359438)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: スカベンジャー受容体 / 放射性分子プローブ / CD36受容体 / SPECT/CT / in vivoイメージング

Outline of Final Research Achievements

Oxidized LDL (oxLDL), which is recognized by scavenger receptors (SR), was labeled with radioiodine and the expression level of SR in tissues was quantitatively evaluated in in vivo/ex vivo studies.
When radiolabeled oxLDL was injected intravenously into normal mice, a characteristic accumulation of radioactivity in brown fat was observed, and CD36, one of SRs, was profoundly involved in this distribution. On the other hand, when using tumor-bearing mice or atherosclerosis model mice, accumulation of radioactivity in the lesion sites was indicated to be dependent on the CD36 expression.
SR directly participates in the removal of waste products, and the breakdown of SR function would be a cause of various diseases. It is expected that quantitative analysis and the development of therapeutic molecules targeting CD36 will lead to the diagnosis as well as prevention of related diseases.

Free Research Field

放射性分子プローブ

Academic Significance and Societal Importance of the Research Achievements

褐色脂肪組織がCD36受容体を介して酸化LDLを能動的に取り込むことを明らかにし、同組織が「生体内老廃物の除去」という機能を有している可能性が示された。また、CD36受容体は骨格筋にも発現しているため、「運動が健康の増進に繋がる」という既成概念に対して科学的な根拠を導くことで、老年症候群（サルコペニア）の予防に向けて新たな知見を提供しうる。
さらに、アテローム性動脈硬化の形成や腫瘍の悪性度にCD36受容体が関与していることを示した本研究成果は、生活習慣病や転移性腫瘍の診断に資するものであり、スカベンジャー受容体の発現と各種疾患との関係性を探った点においても学術的・社会的意義が大きいと考える。