RT Journal Article
SR Electronic
T1 Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti–Fibroblast Activation Protein Antibody Correlates with Severity of Arthritis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 778
OP 783
DO 10.2967/jnumed.114.152959
VO 56
IS 5
A1 Peter Laverman
A1 Tessa van der Geest
A1 Samantha Y.A. Terry
A1 Danny Gerrits
A1 Birgitte Walgreen
A1 Monique M. Helsen
A1 Tapan K. Nayak
A1 Anne Freimoser-Grundschober
A1 Inja Waldhauer
A1 Ralf J. Hosse
A1 Ekkehard Moessner
A1 Pablo Umana
A1 Christian Klein
A1 Wim J.G. Oyen
A1 Marije I. Koenders
A1 Otto C. Boerman
YR 2015
UL http://jnm.snmjournals.org/content/56/5/778.abstract
AB One of the most prominent cell populations playing a role in rheumatoid arthritis (RA) is activated fibroblast-like synoviocytes. Among many other proteins, fibroblast-like synoviocytes dominantly express fibroblast activation protein (FAP). Because of the high expression of FAP in arthritic joints, radioimmunoimaging of activated fibroblasts with anti-FAP antibodies might be an attractive noninvasive imaging tool in RA. Methods: SPECT and PET with 111In- and 89Zr-labeled anti-FAP antibody 28H1 was performed in mice with CIA. The radioactivity uptake in joints was quantified and correlated with arthritis score. Results: Both 111In-28H1 and 89Zr-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 111In-28H1 ranged from 2.2 percentage injected dose per gram (%ID/g) in noninflamed joints to 32.1 %ID/g in severely inflamed joints. DP47GS accumulation ranged from 1.6 %ID/g in noninflamed tissue to 12.0 %ID/g in severely inflamed joints. Uptake of 28H1 in inflamed joints correlated with arthritis score (Spearman ρ, 0.69; P < 0.0001) and increased with severity of arthritis. Conclusion: SPECT/CT imaging with the anti-FAP antibody 111In-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. 89Zr-28H1 was less favorable for RA imaging because of an elevated bone uptake of 89Zr. Future studies will focus on the potential role of 28H1 as a tool to monitor therapy response early on.