期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 40, 期 1, 页码 125-132出版社
SPRINGER
DOI: 10.1007/s00259-012-2261-2
关键词
PET probes; Tau; Amyloid; Alzheimer's disease
资金
- NEDO in Japan
- Ministry of Health, Labor, and Welfare of Japan
- [23390297]
- Grants-in-Aid for Scientific Research [12J07785, 23390235, 22390228, 23390297, 23591735] Funding Source: KAKEN
Extensive deposition of senile plaques and neurofibrillary tangles in the brain is a pathological hallmark of Alzheimer's disease (AD). Although several PET imaging agents have been developed for in vivo detection of senile plaques, no PET probe is currently available for selective detection of neurofibrillary tangles in the living human brain. Recently, [F-18]THK-523 was developed as a potential in vivo imaging probe for tau pathology. The purpose of this study was to compare the binding properties of [F-18]THK-523 and other amyloid imaging agents, including PiB, BF-227 and FDDNP, to synthetic protein fibrils and human brain tissue. In vitro radioligand binding assays were conducted using synthetic amyloid beta(42) and K18 Delta K280-tau fibrils. Nonspecific binding was determined by the addition of unlabelled compounds at a concentration of 2 mu M. To examine radioligand binding to neuropathological lesions, in vitro autoradiography was conducted using sections of AD brain. [F-18]THK-523 showed higher affinity for tau fibrils than for A beta fibrils, whereas the other probes showed a higher affinity for A beta fibrils. The autoradiographic analysis indicated that [F-18]THK-523 accumulated in the regions containing a high density of tau protein deposits. Conversely, PiB and BF-227 accumulated in the regions containing a high density of A beta plaques. These findings suggest that the unique binding profile of [F-18]THK-523 can be used to identify tau deposits in AD brain.
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