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The present invention relates to the field of diagnostic imaging of Alzheimer's disease and provides compounds useful in such diagnostic imaging, as well as methods for their preparation and use. Alzheimer's disease is the fourth most common cause of death in the western world, after heart disease, cancer and strokes. In the USA there are approximately 4 million people suffering with Alzheimer's disease, at an annual cost of $100 billion. Therefore, the cost per person in the USA is $25,000 per year. There are currently 20 million sufferers of dementia in the world. This is set to double to 40 million by the year 2025 as the number of people aged 65 doubles from 390 million now to 800 million in 2025. Of these 40 million, approximately 56 percent will be suffering from Alzheimer's disease, accounting for 22.2 million. The in vivo imaging techniques used at present do not in all cases differentiate the diagnosis of Alzheimer's disease from other forms of dementia. The differential diagnosis of patients will become increasingly important as more treatments become available. Imaging agents will also be required to image Alzheimer patients at earlier stages of the disease to allow preventive treatment, and for monitoring disease progression. Currently the only definitive test for Alzheimer's disease is examination of the brain at autopsy for the presence of distinctive pathophysiologies. One of the most widely acknowledged of these pathophysiologies is the presence of senile plaques in brain tissue. Senile plaques are deposits of a 40-43 amino acid protein called the ?-amyloid protein. They are an early and invariant aspect of the disease and it is thought that the deposition of ?-amyloid occurs some time prior to the onset of clinical symptoms. Amyloid-specific radiotracers have been suggested as potential
imaging agents for Alzheimer's disease. Congo Red has been demonstrated
to be an effective binder of ?-amyloid, but does not cross the blood-brain
barrier (BBB) well (Klunk et al 1994 Neurobiology of Aging Vol. 15 pp.
691-698). There is no convincing functional evidence that abnormalities
in the BBB reliably exist in Alzheimer's (Kalaria 1992, Cerebrovascular
and Brain Metabolism Reviews, Vol 4, p 226). Therefore, an important property
of an Alzheimer's in vivo imaging agent is that it crosses the BBB. U.S.
Pat. No. 3,947,470 and U.S. Pat. No. 4,024,273 describe certain benzofuran
compounds having coronary vasodilator activity. Howlett et al (Biochem
J. (1999), 340, 283-9) describes a series of benzofuran derivatives which
are inhibitors of fibril formation in the ?-amyloid peptide. The aim of
the present invention is the provision of novel 99m Tc-labelled agents
for in vivo imaging of Alzheimer's disease. To be able to successfully
image Alzheimer's disease in vivo, an agent must be capable of crossing
the BBB as well as binding to ?-amyloid.
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