Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Teeter, Matthew G.

2nd Supervisor

Thiessen, Jonathan D.

Co-Supervisor

Abstract

Osteoarthritis (OA) is a joint disease that causes pain, stiffness, and loss of function. Inflammation of the synovium plays a role in the pathology of OA. Macrophages are the dominant immune cells in synovial tissue. Activated macrophages over-express the translocator protein (TSPO). [18F]FEPPA is a 2nd generation positron emission tomography (PET) tracer that can target TSPO with high specificity. Hybrid [18F]FEPPA PET/MRI may enable accurate quantification of macrophage activity in vivo. In this work, [18F]FEPPA tracer uptake in knee synovial tissue was measured ex vivo using autoradiography and was validated to correlate to the true macrophage activity determined by immunofluorescence (IF). A clinical [18F]FEPPA PET/MRI protocol showed similar ability to quantify macrophage activation in vivo. This study suggests that [18F]FEPPA PET/MRI may be an effective tool to investigate the role of inflammation in the pathology of OA or to validate the efficacy of future anti-inflammatory OA treatments.

Summary for Lay Audience

Osteoarthritis (OA) is the most common joint disease affecting nearly 4 million Canadians. Knee OA causes symptoms of pain and stiffness, leading to a decrease in mobility and quality of life. Pain in OA is usually caused by thinning of a smooth surface that lines the bones in the knee called cartilage. When the cartilage becomes too thin, knee bones begin to rub together and cause pain. Recent studies have shown a link between the body’s inflammation response and the loss of cartilage. We need a better understanding of how inflammation relates to the start of OA to be able to develop effective treatments. A new agent that can target inflammation called [18F]FEPPA has been developed and may be useful to learn more about how inflammation affects OA. The goal of this work was to verify that [18F]FEPPA could be used accurately to measure inflammation in the knee, without the need to take a sample of diseased tissue.

An experiment was designed to scan the inflammation in knees of patients with OA who were scheduled to have knee replacement surgery. The results from the scan were compared to measurements of inflammation taken directly from tissue removed during the patient’s knee replacement surgery. The results showed that scanning patients’ knees with [18F]FEPPA was able to accurately measure their knee inflammation. This scanning method could allow researchers to find new ways to treat OA by coming up with new drugs that can reduce inflammation in the knee and reverse the course of the disease. Researchers may also be able to use this scan to find connections between inflammation in joints and our gut health or the development of stiff joints as we age.

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