Synthesis and amyloid binding properties of rhenium complexes: Preliminaryprogress toward a reagent for SPECT imaging of Alzheimer's disease brain

The definitive diagnosis of Alzheimer's disease (AD) requires the detection of amyloid plaques in postmortem brain. Although the amount of fibrillar a myloid roughly correlates with the severity of symptoms at the time of deat h, the temporal relationship between amyloid deposition, neuronal loss, and cognitive decline is unclear. To elucidate this relationship, a noninvasiv e, practical method for the quantitation of brain amyloid deposition is req uired. We describe herein the initial stages of a strategy to accomplish th is goal by single photon computed tomographic imaging. The amyloid-binding dye Congo Red was modified to allow its conjugation to the monoamine-monoam ide bis(thiol) ligand. This ligand complexes technetium(V) in its neutral o xo form. A biphenyl-containing building block was conjugated to the protect ed ligand, and the product was coupled to the relevant aromatic compounds. Rhenium oxo complexes, which are isosteric, but nonradioactive, analogues o f the potential imaging agent technetium oxo complexes, were synthesized. T hese complexes bound to A beta amyloid fibrils produced in vitro and staine d amyloid plaques and vascular amyloid in AD brain sections.