Fluorinated PET Tracers for Alzheimer’s Disease

Alzheimer's Disease (AD) is a progressive, neuro-degenerative disorder of the brain, and the most common form of dementia among the elderly population.  The major hallmarks of AD are the presence of two characteristic abnormal protein aggregates: extraneuronal beta-amyloid plaques and intraneural neurofibrillary tangles. Together, these constitute biomarkers of AD. To date there is no cure for AD, but there are drug treatments that can slow disease progression.  Therefore, early and differential diagnosis (for example, cf. vascular dementia) would be beneficial.  The evaluation of beta-amyloid load in the brain with non-invasive techniques such as PET may enable prodromal detection of AD. Researchers at the University of Aberdeen have developed novel compounds derived from the sedative 5,5-disubstituted barbiturates class as potential PET radiotracers.  This compound class has a number of advantages:

• Very good capacity to cross the blood-brain-barrier in humans and animals
• Excellent ability to chelate metals, including zinc
• Very good ability to form supramolecular structures

Radiolabelled barbiturates could therefore bind to plaques and tangles after crossing the blood-brain-barrier. We have synthesised cold and hot tracer molecules and have demonstrated binding to amyloid plaques in the brain, and discrimination of amyloid-expressing from wild-type mice.

Benefits

• Rapid and good brain uptake
• Affinity between tracer and amyloid protein
• Good clearance after 1 hour
• Ease of synthesis
• Ease of labelling with 18F
• No side effects and good recovery

Applications

• Novel class of PET ligands for pre-clinical and clinical studies
• Monitoring of disease stage and disease progression
• Monitoring of Alzheimer’s Disease and other neurodegenerative diseases

PCT patent application WO2013038153