Development of novel PET ligands for p62/SQSTM1

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19872
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Ono Maiko 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 研究員(任常) (70595876)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ポジトロン断層撮影（PET） / イメージング / オートファジー / p62 / 神経変性疾患 / 疾患マーカー

Outline of Final Research Achievements

p62/SQSTM1 is a substrate for selective autophary, and colocalized with abnormal protein aggregates formed in the brain of various neurodegenerative disease. In vivo imaging technology for visualization of p62 accumulation in the living brain provide cross-pathological markers of neurodegenerative disease. In this study, we developed a novel positron emission tomography (PET) imaging ligands for p62. Two of our candidate compounds were confirmed to bind to p62 in biomolecular interaction analysis and a cultured cell-based assay, respectively. Further, one candidate showed accumulation at abnormal protein aggregates in the brain of neurodegenerative disease mouse model, suggesting that this candidate also binds to p62 in vivo. Further investigations of those candidate compounds found in this study will contribute to the creation of useful p62 PET imaging agents.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究で見いだされたp62 PETプローブ候補化合物は、p62の蓄積を生体内で画像化する分子イメージング技術の創製に寄与し得る。開発を行ったPETプローブはヒトでの応用が可能であり、様々な神経変性疾患の疾患横断的スクリーニングを可能にする新たなツールへの発展が期待される。