Development of Alzheimer's disease imaging agents for clinical studies

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of neurotransmitters, as well as acetylcholinesterase and nicotinic acetylcholine receptors in the central nervous system that leads to learning and memory deficits, among other problems. The disease is associated with increased production and accumulation extracellular amyloid plaques and neurofibrillary tangles in aging human brain, shown in postmortem exams. New methods for reliable in vivo measurement of brain therefore would be much more ideal. PET and SPECT imaging are sensitive methods for the quantitation of AD biomarkers. The development of molecular imaging agents for AD is critically important in the early diagnosis, neuropathogenesis studies and treatment of AD. A number of potential diagnostic PET and SPECT imaging agents targeting AD have been synthesized and evaluated. Although many agents showed excellent results for in vitro monitoring of the disease, there are only several radioligands with high selectivity and specificity to binding sites and appropriate pharmacokinetics, such as [11C]MP4A, [11C]PMP, [11C]nicotine, 2- or 6-[18F]fluoro-A-85380, [11C]SB-13, [11C]PIB, and [18F]FDDNP, that have been tested in AD patients. Here we review some recent progress and development of AD imaging agents using PET and SPECT in human clinical studies.