AMicro-SPECT/CTSystemfor ImagingofAA-Amyloidosis in Mice

Amyloidosis refers to a diverse group of diseases characterized by the abnormal extracellular deposition of proteinaceous substances within the body’s organs and tissues. The protein substances are known as amyloid and consist of insoluble fibrils. In general, amyloid deposits arise due to the overproduction of an amyloidogenic protein or as a result of a genetic mutation that occurs in a normally soluble, innocuous, protein that renders it amyloidogenic. Amyloid deposits have been found in virtually every organ and tissue and may be of a restricted localized form or systemic and involve multiple organ or tissue systems. More than 20 proteins have been identified as components of pathologic amyloid deposits, including the A(β) peptide in Alzheimer’s disease; amylin in Type-2 diabetes; and the prion protein in the spongiform encephalopathies such as mad cow disease. Our focus is on AAand AL-amyloidosis, which respectively are composed of apolipoprotein A synthesized during chronic inflammation and immunoglobulin light chains synthesized by abnormal plasma cells. The understanding of amyloid, its structure and biology, has advanced with the available technology [Sipe and Cohen, 2000]. The term amyloid (meaning starchlike) was coined in 1854 when a macroscopic brain tissue abnormality was found to have staining characteristics similar to cellulose when treated with iodine. Many years later, studies revealed that amyloid-burdened organs and tissues exhibited birefringence when stained with the cotton dye Congo red; that is, when viewed microscopically through crossed polarizers, there is a striking change in color in the amyloid-bound dye from red to apple green. This test is still used to diagnose the disease. Subsequently, electron microscopic analysis showed that amyloid deposits contain rigid, non-branching fibrils (10 nm in diameter). Further chemical analysis