title: Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti-Fibroblast Activation Protein Antibody Correlates with Severity of Arthritis.
abstract: 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 (111)In- and (89)Zr-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 (111)In-28H1 and (89)Zr-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 (111)In-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.
  
  
  CONCLUSIONS
  SPECT/CT imaging with the anti-FAP antibody (111)In-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. (89)Zr-28H1 was less favorable for RA imaging because of an elevated bone uptake of (89)Zr. Future studies will focus on the potential role of 28H1 as a tool to monitor therapy response early on.
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands peter.laverman@radboudumc.nl.
authors: Peter
authors: P
authors: Laverman
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Tessa
authors: T
authors: van der Geest
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Department of Imaging Chemistry and Biology, King's College London, London, United Kingdom.
authors: Samantha Y A
authors: SY
authors: Terry
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Danny
authors: D
authors: Gerrits
authors: Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Birgitte
authors: B
authors: Walgreen
authors: Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Monique M
authors: MM
authors: Helsen
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Basel, Basel, Switzerland; and.
authors: Tapan K
authors: TK
authors: Nayak
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Anne
authors: A
authors: Freimoser-Grundschober
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Inja
authors: I
authors: Waldhauer
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Ralf J
authors: RJ
authors: Hosse
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Ekkehard
authors: E
authors: Moessner
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Pablo
authors: P
authors: Umana
authors: Roche Pharmaceutical Research and Early Development, Innovation Center Zurich, Schlieren, Switzerland.
authors: Christian
authors: C
authors: Klein
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Wim J G
authors: WJ
authors: Oyen
authors: Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Marije I
authors: MI
authors: Koenders
authors: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Otto C
authors: OC
authors: Boerman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D010450:Endopeptidases; D005347:Fibroblasts / Q000000981:diagnostic imaging; D018093:Gelatinases / Q000276:immunology*; D007205:Indium Radioisotopes; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D012697:Serine Endopeptidases / Q000276:immunology*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed; D015040:Zirconium; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000911:Antibodies, Monoclonal; D010450:Endopeptidases; D018093:Gelatinases; D007205:Indium Radioisotopes; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D015040:Zirconium; D000099167:Fibroblast Activation Protein Alpha
keywords: CIA; PET imaging; SPECT imaging; fibroblast activation protein (FAP); monoclonal antibody