Development of novel imaging agents for the prospective quantification of joint damage to reduce animal numbers in osteoarthritis research

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Osteoarthritis (OA) is the most common form of arthritis and a leading cause of pain and disability, where there is progressive loss of joint function due to continual erosion and remodelling of the tissues of the joint. There are currently no modifying treatments for disease and patients rely on simple pain killers and ultimately joint replacement surgery. Investigating the pathways that cause disease has been very challenging as the human condition is very variable in its course, it is difficult to obtain tissues from patients (except at joint replacement surgery) and we currently have no ways of detecting early disease. Animal models of OA have significant utility because disease can be studied at all stages of the condition, tissues are readily available, and the onset of disease is known. In the past 10 years a number of advances have arisen from the use of mouse models of OA induced by surgical joint destabilisation. Combining these models with mice that have genetic modification has revealed several key pathways/molecules important for the OA process. Many academic and pharmaceutical companies use these models for such investigations. Progress in developing novel treatments for OA is very likely to arise from pre-clinical models.Evaluation of joint damage both in the clinic and in animal models of OA is hampered by the inability to image cartilage accurately and non-invasively. X-ray radiographs measure cartilage loss by a reduction in the joint space, thus are only able to pick up relatively advanced disease. In animal models, joint damage is typically assessed by histology after sacrificing the animals at regular intervals throughout studies (usually 4-12 weeks). The latter increases the number of animals used in each study by the number of time points required. A non-invasive imaging method that would be able to visualise the degradation of the articular cartilage over time would greatly reduce the numbers of animals being used in arthritis research. Such a system, being quantitative, might also increase the reliability of measurements and thus also reduce numbers. We have already demonstrated that it is possible to tag cartilage specific molecules to visualise the cartilage specifically. In this project, we will develop a novel imaging agent that can be combined with microCT scanning to create a sensitive, quantitative cartilage assessment tool in OA. This will initially dramatically reduce the number of animals used per OA study and is potentially translatable into a clinical imaging agent for early OA in humans.