18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease

被引：257

作者：

Harada, Ryuichi ^{[1
]}

Okamura, Nobuyuki ^{[1
,2
,3
]}

Furumoto, Shozo ^{[4
]}

Furukawa, Katsutoshi ^{[5
]}

Ishiki, Aiko ^{[5
]}

Tomita, Naoki ^{[5
]}

Tago, Tetsuro ^{[4
]}

Hiraoka, Kotaro ^{[3
]}

Watanuki, Shoichi ^{[3
]}

Shidahara, Miho ^{[3
,6
]}

Miyake, Masayasu ^{[3
]}

Ishikawa, Yoichi ^{[4
]}

Matsuda, Rin ^{[3
]}

Inami, Akie ^{[3
]}

Yoshikawa, Takeo ^{[2
]}

Funaki, Yoshihito ^{[4
]}

Iwata, Ren ^{[4
]}

Tashiro, Manabu ^{[3
]}

Yanai, Kazuhiko ^{[2
]}

Arai, Hiroyuki ^{[5
]}

Kudo, Yukitsuka ^{[1
,4
]}

机构：

[1] Tohoku Univ, Inst Dev Aging & Canc, Div Neuroimaging, Sendai, Miyagi 980, Japan

[2] Tohoku Univ, Sch Med, Dept Pharmacol, Sendai, Miyagi 980, Japan

[3] Tohoku Univ, Ctr Cyclotron & Radioisotope, Div Cyclotron Nucl Med, Sendai, Miyagi 980, Japan

[4] Tohoku Univ, Ctr Cyclotron & Radioisotope, Div Radiopharmaceut Chem, Sendai, Miyagi 980, Japan

[5] Tohoku Univ, Inst Dev Aging & Canc, Dept Geriatr & Gerontol, Sendai, Miyagi 980, Japan

[6] Tohoku Univ, Sch Med, Div Med Phys, Sendai, Miyagi 980, Japan

来源：

JOURNAL OF NUCLEAR MEDICINE | 2016年 / 57卷 / 02期

关键词：

Alzheimer's disease; tau; PET; radiotracer; F-18-THK5351; TAU-PATHOLOGY; TANGLES; BETA; DERIVATIVES; C-11-PIB; PLAQUES;

D O I：

10.2967/jnumed.115.164848

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel-tau PET tracer, F-18-THK5351, through compound optimization of arylquinoline derivatives. Methods: The in vitro binding properties, pharmacokinetics, and safety of F-18-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. Results: F-18-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white matter tissue than did F-18-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, F-18-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than F-18-THK5117. Conclusion: F-18-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.

引用

页码：208 / 214

页数：7

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