A novel PET imaging method may improve evaluation of joint inflammation in rheumatoid arthritis (RA) patients by targeting translocator protein (TSPO) expression in joint lining tissue, according to research published online in the July issue of The Journal of Nuclear Medicine.
The first of its kind analysis demonstrates how TSPO PET may be used an as imaging tool of macrophages, or immune cells responding to inflammation, and a cell group that plays a critical role in rheumatoid arthritis inflammation known as synovial fibroblasts.
"TSPO-targeted imaging has long been used as a means of imaging macrophage infiltration in vivo," said lead author Nehal Narayan, PhD, of the Botnar Research Centre at the University of Oxford, in a prepared statement. "Numerous studies have demonstrated TSPO-targeted PET as a highly sensitive and specific means of imaging synovitis (inflammation of joint lining tissue), purportedly through imaging synovial macrophage infiltration, a critical process in RA pathogenesis. However, this premise does not take into account the ubiquitous expression of TSPO."
Narayan and colleagues examined cellular expression of TSPO in the synovial tissue of six rheumatoid arthritis patients and six healthy volunteers that underwent PET scans of both knees using TSPO radioligand carbon-11 (11C)-PBR28. TSPO mRNA expression and hydrogen-3 (3H)-PBR28 radioligand binding were evaluated using in vitro monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T-lymphocytes, according to the researchers.
Overall, the researchers found a higher 11C-PBR28 PET signal in the joints of patients with RA. Moreover, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA patients compared to healthy controls.
Additionally, immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells and in vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding in activated FLS, non-activated and activated M2 reparative macrophages, the researchers wrote. The lowest TSPO expression was in activated and non-activated CD4+ T lymphocytes.
"TSPO PET imaging in early phase clinical trials may provide a sensitive indication of treatment response to such novel therapies with a view to informing the design of later stage clinical trials," Narayan said. "As our knowledge of cellular TSPO expression and behavior grows, TSPO-targeted imaging may also give us unique insights into the pathogenesis of inflammatory disease."