New PET tracer detects inflammatory arthritis before symptoms appear

Rheumatoid arthritis is the most common type of inflammatory arthritis and affects 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, disabilities, loss of function, decreased quality of life, and possibly shortened life expectancy.

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

CD69 is one of the earliest cell surface markers seen on cells experiencing inflammation and is present in the tissue of patients with active rheumatoid arthritis. As such, researchers evaluated the performance of the CD69-targeting PET agent, ⁶⁸Ga-DOTA-Z_CAM241, for early disease detection in a mouse model of inflammatory arthritis.

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

Increased uptake of the CD69-directed tracer ⁶⁸Ga-DOTA-Z_CAM241 was seen 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 uptake of ⁶⁸Ga-DOTA-Z_CAM241 also correlated with the clinical score and disease severity. The nonspecific control peptide demonstrated only low binding.

^"68Ga-DOTA-Z_CAM241 is a potential candidate for PET imaging of activated immune cells during rheumatoid arthritis onset," stated Olof Eriksson, PhD, associate professor and group leader of Translational PET Imaging at the Department of Medicinal Chemistry at Uppsala University, in Uppsala, Sweden. "We know that physicians are asking for better methods to image inflammation, for example in rheumatoid arthritis, and we hope this technology will be broadly used in many diseases that involve activated immune cells and inflammation.