NL
DE
Rheumatoid arthritis is one of the most prevalent and debilitating joint diseases worldwide and is characterized by synovial inflammation, which is linked to the development of joint destruction. MRI and ultrasonography are widely being used to detect synovial inflammation. However, these techniques can only show the extent of inflammation, rather than the activation status of inflammatory cells such as macrophages that play a crucial role in synovial inflammation and joint destruction.
Together, Wessel Theeuwes and Irene Di Ceglie set out to develop a molecular imaging modality for CD64 (Fc gamma receptor (FcγR)I), which is considered as macrophage activation marker, using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovial inflammation using optical and nuclear imaging. In this project, led by Martijn van den Bosch and Peter van der Kraan of the Experimental Rheumatology lab, the researchers tightly collaborated with the Department of Medical Imaging and GlaxoSmithKline.
They showed that CD64 is expressed in synovium of early and late-stage rheumatoid arthritis patients and correlates with factors known to be involved in disease progression including various pro-inflammatory cytokines and matrix-degrading enzymes. Ex vivo and in vivo studies were employed to research the potential of CD64 as novel imaging marker for the extent and phenotype of synovial inflammation in rheumatoid arthritis.
The researchers implemented an in vivo design using immunodeficient mice that accept human tissue implants and allow development of a human imaging tracer. They reported that the ratio of uptake of the anti-CD64 antibody in these implanted human rheumatoid arthritis synovial explants over blood was significantly higher when compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding. They hope his study forms one of the stepping stones needed for the development of novel imaging tracers that can be used to monitor the joint-destructive nature of the synovial inflammation and response to treatment in rheumatoid arthritis patients.
Read the study here.
Theeuwes WF, Di Ceglie I, Dorst DN, Blom AB, Bos DL, Vogl T, Tas SW, Jimenez-Royo P, Bergstrom M, Cleveland M, van der Kraan PM, Laverman P, Koenders MI, van Lent PL, van den Bosch MHJ. CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis. Arthritis Res Ther. 2023 Aug 31;25(1):158. doi: 10.1186/s13075-023-03147-y. PMID: 37653557; PMCID: PMC10468866.
