In Situ Imaging of Collagen Degradation Activity in Multiple Myeloma and Lung Fibrosis Murine Models Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive pathologic remodeling during many life-threatening diseases such as cancer, fibrosis and a variety of auto-immune diseases (e.g. rheumatoid arthritis). Since tissue specific collagen remodeling activity is known to correlate with the disease stages, in situ imaging of such activity can inform disease condition and efficacy of therapeutic treatment. This is particularly true if image can report the active state of the disease similar to the functional brain imaging. In the proposed work, based on exciting preliminary data, we plan to develop a series of end templated collagen hybridizing peptides (CHPs) probes that can facilitate accurate imaging of collagen degradation activity within hours after injection with clearance time less than a day, ideal for routine animal imaging.
In Aim 1, we will design and synthesize various dimeric CHPs that have low tendency to self trimerize but can hybridize to denatured collagen at fast binding rate and enhanced clearance from the target site.
In Aim 2, we will develop multiple myeloma and lung fibrosis murine disease models, and demonstrate dimeric CHP's use in assessing the disease states. Since ECM degeneration is directly related to the debilitating symptoms of patients and the cost of healthcare system, a new strategy that can be used in animal models to probe the ECM remodeling could revolutionize development of new therapy benefiting the patient and the society. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
In Situ Imaging of Collagen Degradation Activity in Multiple Myeloma and Lung Fibrosis Murine Models During many life-threatening diseases, collagen, the most abundant proteins in the body, undergoes extensive pathological remodeling. Since collagen remodeling activity correlates with the disease stages, tissue specific assessment of such activity in live animal model can provide precise information about the disease progression and efficacy of therapeutic treatment. The proposed study is aimed at developing in vivo animal imaging methods based on a specific probe that can target degraded collagen and report the severity and location of multiple myeloma and lung fibrosis. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page
