PT  - JOURNAL ARTICLE
AU  - Peter Laverman
AU  - Tessa van der Geest
AU  - Samantha Y.A. Terry
AU  - Danny Gerrits
AU  - Birgitte Walgreen
AU  - Monique M. Helsen
AU  - Tapan K. Nayak
AU  - Anne Freimoser-Grundschober
AU  - Inja Waldhauer
AU  - Ralf J. Hosse
AU  - Ekkehard Moessner
AU  - Pablo Umana
AU  - Christian Klein
AU  - Wim J.G. Oyen
AU  - Marije I. Koenders
AU  - Otto C. Boerman
TI  - Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti–Fibroblast Activation Protein Antibody Correlates with Severity of Arthritis
AID  - 10.2967/jnumed.114.152959
DP  - 2015 May 01
TA  - Journal of Nuclear Medicine
PG  - 778--783
VI  - 56
IP  - 5
4099  - http://jnm.snmjournals.org/content/56/5/778.short
4100  - http://jnm.snmjournals.org/content/56/5/778.full
SO  - J Nucl Med2015 May 01; 56
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.