ImmunoPET and immunoSPECT of rheumatoid arthritis with radiolabeled anti-fibroblast activation protein (FAP) antibody correlates with severity of arthritis

P. Laverman, T. van der Geest, S. Terry, D. Gerrits, B. Walgreen, M. Helsen, T. Nayak, A. Freimoser-Grundschober, I. Waldhauer, R. Hosse, E. Moessner, P. Umana, C. Klein, W. Oyen, M. Koenders and O. Boerman

Radboud University Medical Center, Netherlands;
May, 2015



One of the most prominent cell populations playing a role in rheumatoid arthritis (RA) is activated fibroblast-like synoviocytes (FLSs). Among many other proteins, FLSs dominantly express fibroblast activation protein (FAP). Due to high expression of FAP in arthritic joints, radioimmunoimaging of activated fibroblasts with anti-FAP antibodies might be an attractive non-invasive imaging tool in RA.Single photon emission computed tomography (SPECT) and positron emission tomography (PET) with In-111- and Zr-89-labeled anti-FAP antibody 28H1 was performed in mice with collagen-induced arthritis. Radioactivity uptake in joints was quantified and correlated with arthritis score.Both In-111-28H1 and Zr-89-28H1 showed high uptake in inflamed joints, being 3-fold higher than that of the irrelevant isotype-matched control antibody DP47GS, clearly indicating specific accumulation of 28H1. Uptake of In-111-28H1 ranged from 2.2 \%ID/g in non-inflamed joints to 32.1 \%ID/g in severely inflamed joints. DP47GS accumulation ranged from 1.6 \%ID/g in non-inflamed tissue to 12.0 \%ID/g in severely inflamed joints. Uptake of 28H1 in inflamed joints correlated with arthritis score (Spearman's �? 0.69, p<0.0001) and increased with severity of arthritis.SPECT/CT imaging with the anti-FAP antibody In-111-28H1 specifically visualized arthritic joints with high resolution, and tracer accumulation correlated with the severity of the inflammation in murine experimental arthritis. Background uptake of the radiolabeled antibody was low, resulting in excellent image quality. Zr-89-28H1 was less favorable for RA imaging due to an elevated bone uptake of Zr-89. Future studies will focus on the potential role of 28H1 as a tool to monitor therapy response early-on.