New PET tracer detects inflammatory arthritis before symptoms appear

A new PET imaging technique can non-invasively detect active inflammation in the body before clinical symptoms appear, according to a study published in the February issue of The Journal of Nuclear Medicine. Using a PET tracer that binds to proteins on activated immune cells, the technique produces images of ongoing inflammation throughout the body, such as rheumatoid arthritis. This makes it easier for doctors to diagnose and treat patients.

Rheumatoid arthritis is the most common type of inflammatory arthritis, affecting 18 million people worldwide. It is a complex autoimmune disease characterized by chronic inflammation. This inflammation can cause the destruction of cartilage and bone, eventually leading to limitations, disability, loss of function, decreased quality of life, and possibly shortened life expectancy.

“A major interest of the field of rheumatology is using precision diagnostics to predict disease development in people with risk factors for rheumatoid arthritis,” said Fredrik Wermeling, Ph.D., associate professor and head group at the Department of Medicine, Division of Rheumatology, Center for Molecular Medicine (CMM) at Karolinska Institutet, Solna, Sweden. “The hope is to find ways to identify these people before they even get sick, with the goal of being able to treat them so they never develop the disease.”

CD69 is one of the first cell surface markers observed on cells suffering from inflammation and is present in tissues of patients with active rheumatoid arthritis. Thus, the researchers evaluated the performance of the PET agent targeting CD69, ⁶⁸Ga-DOTA-Z_CAM241for early detection of disease in a mouse model of inflammatory arthritis.

In the study, mice were photographed with ⁶⁸Ga-DOTA-Z_CAM241 PET scan before and three, seven and 12 days after arthritis induction. Disease progression was monitored by clinical parameters, such as body weight measurement and paw swelling. The adoption of ⁶⁸Ga-DOTA-Z_CAM241 in the paws was analyzed and after the last PET scan, tissue biopsy samples were analyzed for CD69 expression. A second group of mice received PET scans with a nonspecific control peptide.

Increased adoption of CD69-directed tracer ⁶⁸Ga-DOTA-Z_CAM241 was observed in the paws of mice with induced inflammatory arthritis three days after induction, which preceded the appearance of clinical symptoms five to seven days after induction. The adoption of ⁶⁸Ga-DOTA-Z_CAM241 also correlated with clinical score and disease severity. The nonspecific control peptide demonstrated only weak binding.

“⁶⁸Ga-DOTA-Z_CAM241 is a potential candidate for PET imaging of immune cells activated during the onset of rheumatoid arthritis,” said Olof Eriksson, Ph.D., associate professor and translational PET imaging group leader in the Department of Medicinal Chemistry. from Uppsala University, Uppsala, Sweden. “We know that doctors are asking for better methods to visualize inflammation, for example in rheumatoid arthritis, and we hope this technology will be widely used in many diseases involving activated immune cells and inflammation.”

Provided by the Society for Nuclear Medicine and Molecular Imaging