Radiolabeling to Track TNF Inhibitors May Improve Rheumatoid Arthritis Treatment

Researchers have developed a method of tracking a particular anti-tumor necrosis factor (TNF) through the body, and determined an effective dose.

Bieke Lambert, of the Department of Radiology and Nuclear Medicine at Ghent University in the Netherlands, led the study. TNF inhibitors are an often-used treatment for rheumatoid arthritis (RA) and spondyloarthritis (SpA), but not all patients respond to them.

The authors suggest this lack of response could be attributable to “lower levels of TNF expression, the involvement of other proinflammatory cytokines, and/or the development of neutralizing antibodies against the TNF blocking agent during treatment.”

In order to optimize anti-TNF treatment, a clearer understanding of TNF expression in affected joints at the individual level is necessary. The researchers looked at one particular anti-TNF, certolizumab pegol (CZP). They had 3 goals: track the progress of CZP through the body through a process known as radiolabeling, examine the biodistribution of CZP and create a dosimetric profile it, and to correlate the uptake to the clinical examination of the involved joints.

The present study includes the analysis for 8 patients who were also participating in a larger clinical trial. There were 4 men and 4 women, the median age was 44 years, and no adverse events were recorded. The authors note that evidence exists demonstrating the efficiency of anti-TNF therapies in RA and SpA, as well as psoriatic arthritis. However, they add “CZP differs from other TNF blockers because of its link with polyethylene glycol,” which in animal studies, has shown to improve distribution compared to other TNF inhibitors.

Each of the participants underwent scanning with a double-headed gamma camera. The researchers completed a whole body scan, then the patient was injected with Tc S-HYNIC CZP. Following injection, whole body scans were performed at 1, 4-6, and 24 hours. Urine was collected between scans, and urinary tracer excretion measured. Finally, the researchers assessed the tracer accumulation in the joints using a scoring system.

This is the first study in which radiolabeling of CZP has been reported. The researchers report being able to observe marked tracer accumulation in the affected joints for 24 hours. Using the whole body scans, the authors report observing “high tracer uptake in the bloodpool and liver and less pronounced uptake in the spleen and kidneys.”

Through imaging studies, the most optimal treatments to target disease may be identified, thereby lowering the patient’s exposure to unnecessary treatments. Additionally, the authors say, “the imaging studies open a window on various pathophysiological and pharmacokinetic aspects [of disease].”

The study, entitled “99mTc-Labeled S-HYNIC Certolizumab Pegol in Rheumatoid Arthritis and Spondyloarthritis Patients: a Biodistribution and Dosimetry Study”, was published last month in the European Journal of Nuclear Medicine and Molecular Imaging Research.