Liposomal treatment of experimental arthritis can be monitored non-invasively with radiolabeled anti-FAP antibodies

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder resulting in synovial inflammation. Fibroblast activation protein (FAP) is over-expressed by fibroblast-like synoviocytes in arthritic joints. Radioimmunoimaging with anti-FAP antibodies might be used to monitor therapy response, thus enabling tailored therapy strategies and therapeutic outcomes. The aim of this study was to assess whether radiolabeled anti-FAP antibodies can be used to monitor the efficacy of treatment with prednisolone phosphate containing long-circulating liposomes (PLP-LCL) in a mouse model of arthritis. Collagen-induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated with a single injection of 10 mg/kg PLP-LCL or empty LCL as control. Single photon emission computed tomography (SPECT) and computed tomography (CT) images were acquired 24 h after injection of ^99mTc-labeled succinimidyl-hydrazinonicotinamide (S-HYNIC)-conjugated anti-FAP antibody, 28H1, at 2, 5 and 9 days after treatment. Uptake of ^99mTc-HYNIC-28H1 in all joints was quantified and correlated with macroscopic arthritis scores. Treatment of CIA with PLP-LCL significantly suppressed joint swelling. Already at one day after treatment the macroscopic arthritis scores showed a 50% decrease. Scores further decreased to only 10% of the initial scores at 5 and 9 days post treatment. In contrast, macroscopic scores increased up to 600% in untreated mice at 9 days post injection of empty LCL. ^99mTc-HYNIC-28H1 uptake ranged from 1.5 %ID/g in non-inflamed joints to 22.6 %ID/g in severely inflamed joints. Uptake of radiolabeled 28H1 in inflamed joints (%ID) correlated with arthritis score (Spearman’s ρ 0.77, p<0.0001). Moreover, uptake of ^99mTc-HYNIC-28H1 slightly increased 9 days after therapy, which was not seen macroscopically, indicating that SPECT/CT imaging might be more sensitive compared to the macroscopic arthritis scoring method. SPECT/CT imaging with ^99mTc-HYNIC-28H1 specifically monitored response to therapy and tracer accumulation correlated with the severity of inflammation. In addition, imaging is potentially more sensitive than the macroscopic scoring method. This study showed that SPECT/CT with ^99mTc-HYNIC-28H1 can be used to noninvasively monitor the course of CIA in mice.