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Development and validation of ultrasound molecular imaging agents for diabetic kidney disease by measuring bio-molecular interactions聽with a novel, sensitive, homogeneous proximity assay (AlphaScreen鈩�)
Clinical signs of diabetic kidney disease (DKD) manifests years and sometimes decades after the initial diagnosis of diabetes. During this 鈥渟ilent鈥� time, the kidney is undergoing molecular changes that will eventually lead to physical damage. Intercepting the molecular changes with specialized therapies could halt DKD and prevent the progression to end-stage kidney disease. Not all diabetics will proceed to DKD; therefore, a sensitive and specific test is necessary to discern who will eventually develop the disease. Ultrasound molecular imaging is a potential tool for the early diagnosis of DKD that can report on this molecular activity at specific sites in the kidney. The goal of this project is to develop an in vitro assay based on amplified luminescent proximity homogeneous assay screen to produce sensitive and specific targeted microbubbles for DKD. The assay will assess and optimize microbubble ligand-receptor interactions necessary to make the targeted contrast agent. Once the targeted microbubbles are developed, we will compare the optimized to non-optimized targeted microbubbles in preclinical models of DKD to assess improvement. The result will be an assay to quickly generate new targeted microbubbles for ultrasound molecular imaging. Ultimately, ultrasound molecular imaging will provide a screening tool for clinicians to detect which diabetic patients will progress to DKD and offer an opportunity for timely intervention.

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