(provided by application): High resolution imaging is becoming an invaluable tool in biomedical research much as it has to the clinician. In the clinic, imaging offers a precise, non-invasive means of diagnosis and directly influences both the therapeutic approach and prognosis. Unfortunately, the development of high-resolution imaging tools demanded by researchers has lagged behind that of the clinic; thus, characterization of the kinetics of in vivo pathology and the subsequent development of novel, effective therapeutics has been hampered. This is particularly true in the field of amyloid- related diseases which include Alzheimer's disease, type I1 diabetes and primary (AL) amyloidosis. It is impossible to fully appreciate and understand the complexity of these diseases, and the means by which they may be halted, without the ability to perform longitudinal studies in individual animals in vivo. To that end, the development high- resolution micro-imaging technologies capable of detecting and quantifying amyloid deposits in vivo is warranted and imperative. We intend to address these important issues through the design and application of a powerful new dual-modality imaging technology, microSPECT, combined with microCT, supported by state-of-the-art 3-D image reconstruction and analysis software. This new technology will be employed to identify radiolabeled amyloid ldeposits in live animals and present the amyloid distribution within the context of a high-resolution CT image of the 1 visceral terrain. With this technology, the goal of quantifying organ-specific amyloid burden in vivo is attainable. The goals are thus to: (i) Complete the design and implementation of a high-resolution, small-animal speciJic dual lSPECT/CT imaging system. (ii). Develop a system of amyloid quantijkation in which microSPECT image data can be directly correlated to amyloid burden. (iii) Use these technologies to study the progression of systemic AA- amyloidosis in two murine models and the regression thereof in response to novel immunotherapies. This study will not only result in technological advancements in the field of small-animal imaging and amyloid-specific radio- tracers but will also provide a wealth of information on the natural progression of amyloidosis in vivo and establish a paradigm for the screening of therapeutic drugs in animal models of human disease. Furthermore, the translation of amyloid-specific imaging technologies will yield tangible clinical benefit.
