Precise evaluation and optimization of the THK probe for tau imaging

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293259
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: FURUMOTO SHOZO 東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198)
• Co-Investigator(Renkei-kenkyūsha): OKAMURA Nobuyuki 東北大学, 大学院医学系研究科, 准教授 (40361076) ; SHIDAHARA Miho 東北大学, 大学院医学系研究科, 講師 (20443070)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: タウ / PET / イメージング / 18F

Outline of Final Research Achievements

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Abnormal deposition of phosphorylated tau is one of the key pathological changes in the AD brain. The purpose of this study is to optimize the chemical structure of THK tau PET probes that have been developed by us for imaging tau pathology in the AD brain with PET. One modification of the probe structure was replacement of the benzene ring to pyridinyl one. Another change was conformational optimization of the fluoropropanol side chain. S-enantiomer of the pyridinyl derivative showed better brain pharmacokinetics in normal mice. The optimized derivative indicated lower non-specific binding to white matter of the AD brain tissue samples. Clinical PET study using the optimized probe demonstrated that higher radioactivity uptakes were observed in the parahippocampal gyrus and inferior temporal gyrus. These results suggest the potential utility of the optimized THK tau probe.

Free Research Field

放射性医薬品学