Preclinical evaluation of a CD137-targeted PET tracer for detection of inflammatory arthritis

Inflammatory arthritis (IA) is characterized by early T cell activation in synovial tissue, yet noninvasive methods to detect this process are limited. This study evaluated Al[¹⁸F]F-NOTA-BCP137, a CD137-targeted bicyclic peptide PET tracer, for imaging CD137⁺ activated immune cells in two mouse models of IA. CD137 expression was characterized in human RA synovium and arthritic mouse joints by transcriptomics, qPCR, and immunohistochemistry. Tracer specificity was assessed in vitro using activated PBMCs, and immune safety was evaluated in human CD137 transgenic mice. PET imaging was performed in collagen antibody-induced arthritis (CAIA) and ICI-induced arthritis models. CD137 was significantly upregulated in RA synovium and arthritic mouse joints, with expression levels correlating with disease activity and preceding clinical arthritis scores. Al[¹⁸F]F-NOTA-BCP137 demonstrated specific binding to CD137-expressing activated T cells without detectable immune activation. PET imaging revealed significantly higher tracer uptake in arthritic joints compared with controls, with uptake values strongly correlating with arthritis severity and increasing prior to clinical symptom onset. These results indicate that CD137-targeted PET with Al[¹⁸F]F-NOTA-BCP137 enables specific detection of early T cell activation in inflammatory arthritis and warrants further investigation as an imaging approach for early-stage detection of joint inflammation.