Design, Synthesis and Evaluation of Fluorinated PET Radioligands for Detection of Alzheimer's Disease

Alzheimer's disease is a neurodegenerative disorder affecting the brain. It is associated with several microscopic markers including neuritic plaques and neurofibrillary tangles. There is also a reduction of the neurotransmitter acetylcholine and its regulating enzyme acetylcholinesterase but an increase in butyrylcholinesterase, a co-regulator of acetylcholine. Butyrylcholinesterase is found in association with all the neuropathological lesions of Alzheimer's disease. Therefore detection of butyrylcholinesterase is considered as a suitable target for diagnosis and treatment. Our research group is actively investigating avenues of synthesis and evaluation of specific agents for molecular imaging of butyrylcholinesterase. Past research by our group has focused on the development of SPECT imaging agents. However, PET imaging of beta amyloid, found in neuritic plaques, is widely used in the imaging of Alzheimer's disease. However such plaques are nonspecific. Therefore development of fluorine radiolabelled butyrylcholinesterase specific PET molecules must be undertaken. We propose to develop a methodology for radiolabelling carbamate molecules, that are butyrylcholinesterase specific, and evaluating, through enzyme, tissue and animal studies their potential for imaging butyrylcholinesterase and therefore Alzheimer's disease. Early diagnosis of Alzheimer's disease is necessary for initiation of early treatment as new drugs become available. Currently, definite diagnosis of Alzheimer's disease is limited to postmortem examination.