PET and SPECT imaging of rheumatoid arthritis with radiolabeled anti-FAP antibody correlates with severity of arthritis

Objectives Rheumatoid arthritis is an autoimmune disease that results in chronic synovial inflammation. Molecular imgaging techniques might aid in adjusting treatments, ultimately leading to improved therapeutic efficacy. Activated fibroblast-like synoviocytes play an important role in joint destruction. These cells abundantly express fibroblast activation protein (FAP). Here we used an anti-FAP antibody, labeled with ⁸⁹Zr and ¹¹¹In for specific imaging of FAP expression in an experimental model of RA.

Methods Arthritis was induced with collagen in DBA/1J mice. The monoclonal anti-FAP antibody 28H1 with high bivalent affinity for murine FAP (< 1 pM) and human FAP (268 pM) was conjugated with desferoxamine and DTPA and labeled with ⁸⁹Zr and ¹¹¹In. Mice were scanned at 24 and 72 h pi. Mice were euthanized at 72 h pi and tissues of interest were dissected. A separate group was injected with FDG.

Results Both ⁸⁹Zr-28H1 and ¹¹¹In-28H1 showed high uptake in inflamed joints, being 3-4 fold higher than that of the irrelevant isotype-matched control antibody DP47GS, strongly indicating specific accumulation of 28H1. Uptake of ¹¹¹In-28H1 ranged from 3.3 %ID/g in non-inflamed joints to 27.4 %ID/g in severely inflamed joints. DP47GS accumulation ranged from 2.5 %ID/g in non-inflamed tissue to 11.7 %ID/g in severely inflamed joints. Uptake of 28H1 in inflamed joints correlated with arthritis score (r2=0.92) and increased with severity of inflammation. FDG only accumulated in severely inflamed joints. FDG uptake in the joints did not correlate with severity of inflammation (r2=0.36). Both PET/CT and SPECT/CT imaging with ⁸⁹Zr-28H1 and ¹¹¹In-28H1 antibody showed excellent delineation of the inflamed joints at both 24 and 72 h pi.

Conclusions The anti-FAP antibody 28H1 labeled with ⁸⁹Zr or ¹¹¹In showed excellent characteristics for imaging inflamed synovial tissue, and uptake correlated with severity of the inflammation.