Radiotracers for a multi‐target approach to the diagnosis of Alzheimer's disease

Abstract

Development of b-amyloid plaques and neurofibrillary tangles is the hallmark of Alzheimer's disease (AD) and progressively affects the overall functioning of the brain. Noninvasive imaging methods aiding early diagnosis will significantly improve benefits provided by treatments and possibly lead to prevention of AD. We report the development of PET radiotracer methods for b-amyloid plaques and tangles, nicotinic a4b2 receptors, serotonin 5HT1A receptors, dopamine D2/D3 receptors and norepinephrine transporters for the study of AD. This multi-target approach is currently being evaluated in AD transgenic mice models.

Microwave Accelerated Synthesis of PET Image Contrast Agents for AD Research

“…PET imaging offers considerable potential given its high resolution, and the availability of designed image contrast agents which could highlight elevated/depleted levels of key molecular targets associated with AD. To date, examples of AD targeted PET imaging agents can be divided into specific categories: The most widely studied to date are agents which target beta amyloid plaques, which are associated with progression of AD [5]. One of the earliest examples is the agent PIB, which, despite its short half-life (a consequence of the 11C label employed) has been used widely for mapping studies [6].…”

“…Among them is the 4 2 nicotinic receptor, which has been linked with AD progression [9]. The agents nifene, nifrolidine, and 2-A85380 all share a common pyridyl motif, which confers receptor binding and also facilitates chemical synthesis of the agents.…”

“…Another is the serotonin receptor, and agents with affinity to this include MPPF and mefway, which share common backbone functionality [10]. In the case of the dopamine receptor, a number of agents have been studied including fallypride and in the case of the norepinephrine transporter, the agent MFP3 [9,11]. …”