DEVELOPMENT OF A NOVEL MINERAL CONTRAST AGENT FOR ORTHOPAEDIC RESEARCH

Abstract

Osteoporosis is a bone disease that increases the risk of fracture. In normal bone, mineral is resorbed by osteoclasts and replaced with new mineral by osteoblasts in a balanced manner. In osteoporotic bone, the rate of resorption outpaces new bone formation, so the bone degenerates. Osteoporosis is currently diagnosed using dual-emission x-ray absorptiometry (DXA) which measures the density of bone. This technique only provides static information. Magnetic resonance imaging (MRI) is a non-invasive technique that generates a 3-dimensional image. The goal of this project was to prepare and optimize a novel targeted contrast agent, Gadolinium-Alendronate (Gd-ALN), for imaging bone, which consists of the MRI-active metal chelate Gadolinium-DOTA conjugated to the mineral binding bisphosphonate, Alendronate. Gd-ALN was evaluated against fluorescently-labeled Alendronate (FL-ALN) for its selective binding to mineral using natural and tissue engineered samples. Utilization of MRI contrast agents like Gd-ALN, is promising technology to evaluate the efficacy of osteoporosis treatments.