Development of HDAC6 PET imaging probes for proteinopathies

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H07486
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Tago Tetsuro 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50780649)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: PET / HDAC6 / 分子イメージング / プロテイノパチー / 核医学 / 放射性医薬品

Outline of Final Research Achievements

Histone deacetylases (HDACs) are enzymes responsible for lysine deacetylation of histones. In particular, HDAC6 is a unique enzyme that is mainly found in the cytosol and regulates deacetylation of cytosolic proteins including α-tubulin and tau protein. HDAC6 has been implicated in neurodegeneration with abnormal protein accumulation in the brain. Thus, research into the role of HDAC6 with in vivo imaging will facilitate development of drugs targeting HDAC6. Our goal was to develop radiolabeled probes for positron emission tomography (PET) imaging of HDAC6. Two radiolabeled Tubastatin A derivatives were successfully synthesized. However, biological evaluations suggested that brain uptake of these probes were poor. Structural optimization which improves the blood-brain barrier permeability is needed.

Free Research Field

放射性医薬品科学