• Biotechnology

Dementia is the third most common cause of death after cancer and cardiac vascular disorders, and Alzheimer disease (AD) is the most common form of dementia, characterized by progressive memory impairment, disordered cognitive functions, altered behavior, and a decline in language function. The pathological hallmarks of AD are extracellular deposits of beta-amyloid (Abeta) plaques and intracellular neurofibrillary tangles. Currently, the clinical diagnosis of AD is only a probable diagnosis and a histological diagnosis can only be obtained after death. According to the amyloid cascade hypothesis, amyloid deposits constitute a central and initial event in the pathogenesis of AD. Therefore, a tracer agent for positron emission tomography (PET) which specifically binds to these Abeta plaques, will provide an important tool for the non-invasive in vivo diagnosis of AD. Furthermore, it might also be used to predict the development of AD before the onset of dementia and to assess the effect of anti-amyloid therapy.

In our recent studies, we showed that [18F]24, a novel radiofluoro-pegylated phenylbenzoxazole derivative, has several favorable properties: high affinity for Abeta aggregates (Ki = 9.3 nM); easily labeled with 18F for imaging (radiochemical yield of 30%, which is suitable for commercial scale production and distribution; small (MW < 500), lipophilic (measured logD = 3.09), and neutral; good initial brain uptake and fast washout (8.12 % ID/g at 2 min and 3.04 % ID/g at 60 min after iv injection)); lower non-specific binding in white matter as demonstrated by autoradiography in vitro and ex vivo using postmortem AD brain sections and Tg2576 mice. These findings suggest that [18F]24 should be investigated further as a potential PET tracer for imaging Abeta plaques in living brain tissue


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