Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti-Fibroblast Activation Protein Antibody Correlates with Severity of Arthritis

被引:89
作者
Laverman, Peter [1 ]
van der Geest, Tessa [1 ]
Terry, Samantha Y. A. [1 ,2 ]
Gerrits, Danny [1 ]
Walgreen, Birgitte [3 ]
Helsen, Monique M. [3 ]
Nayak, Tapan K. [4 ]
Freimoser-Grundschober, Anne [5 ]
Waldhauer, Inja [5 ]
Hosse, Ralf J. [5 ]
Moessner, Ekkehard [5 ]
Umana, Pablo [5 ]
Klein, Christian [5 ]
Oyen, Wim J. G. [1 ]
Koenders, Marije I. [3 ]
Boerman, Otto C. [1 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Radiol & Nucl Med, NL-6500 HB Nijmegen, Netherlands
[2] Kings Coll London, Dept Imaging Chem & Biol, London, England
[3] Radboud Univ Nijmegen, Med Ctr, Dept Expt Rheumatol, NL-6500 HB Nijmegen, Netherlands
[4] Roche Pharmaceut Res & Early Dev, Innovat Ctr Basel, Basel, Switzerland
[5] Roche Pharmaceut Res & Early Dev, Innovat Ctr Zurich, Schlieren, Switzerland
关键词
fibroblast activation protein (FAP); SPECT imaging; PET imaging; CIA; monoclonal antibody; COLLAGEN-INDUCED ARTHRITIS; STROMAL FIBROBLASTS; MOLECULAR-CLONING; PHASE-I; EXPRESSION; RESOLUTION; CANCER; ALPHA; CELLS; ZR-89;
D O I
10.2967/jnumed.114.152959
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 In-111-and Zr-89-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 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 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., 0.69; P < 0.0001) and increased with severity of arthritis. Conclusion: 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 because of 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.
引用
收藏
页码:778 / 783
页数:6
相关论文
共 33 条
  • [1] Bacac M, 2012, U.S. patent, Patent No. [WO/2012/020006, 2013020006]
  • [2] Baehner M, 2013, U.S. patent, Patent No. [WO/2012/130831, 2012130831]
  • [3] Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes
    Bauer, Stefan
    Jendro, Michael C.
    Wadle, Andreas
    Kleber, Sascha
    Stenner, Frank
    Dinser, Robert
    Reich, Anja
    Faccin, Erica
    Goedde, Stefan
    Dinges, Harald
    Mueller-Ladner, Ulf
    Renner, Christoph
    [J]. ARTHRITIS RESEARCH & THERAPY, 2006, 8 (06)
  • [4] Technetium-99m labelled liposomes to image experimental arthritis
    Boerman, OC
    Oyen, WJG
    Storm, G
    Corvo, ML
    vanBloois, L
    vanderMeer, JWM
    Corstens, FHM
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1997, 56 (06) : 369 - 373
  • [5] Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer
    Brom, Maarten
    Joosten, Lieke
    Oyen, Wim J. G.
    Gotthardt, Martin
    Boerman, Otto C.
    [J]. EJNMMI RESEARCH, 2012, 2 : 1 - 11
  • [6] Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data
    Cha, Ji Hyeon
    Lee, Sang Hoon
    Lee, Sheen-Woo
    Park, Kyeongsoon
    Moon, Dae Hyuk
    Kim, Kwangmeyung
    Biswal, Sandip
    [J]. KOREAN JOURNAL OF RADIOLOGY, 2012, 13 (04) : 450 - 461
  • [7] Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging
    Dijkers, Eli C. F.
    Kosterink, Jos G. W.
    Rademaker, Anna P.
    Perk, Lars R.
    van Dongen, Guus A. M. S.
    Bart, Joost
    de Jong, Johan R.
    de Vries, Elisabeth G. E.
    Lub-de Hooge, Marjolijn N.
    [J]. JOURNAL OF NUCLEAR MEDICINE, 2009, 50 (06) : 974 - 981
  • [8] Invasive fibroblast-like synoviocytes in rheumatoid arthritis - Passive responders or transformed aggressors?
    Firestein, GS
    [J]. ARTHRITIS AND RHEUMATISM, 1996, 39 (11): : 1781 - 1790
  • [9] Radioimmunotherapy of Fibroblast Activation Protein Positive Tumors by Rapidly Internalizing Antibodies
    Fischer, Eliane
    Chaitanya, Krishna
    Wueest, Thomas
    Wadle, Andreas
    Scott, Andrew M.
    van den Broek, Maries
    Schibli, Roger
    Bauer, Stefan
    Renner, Christoph
    [J]. CLINICAL CANCER RESEARCH, 2012, 18 (22) : 6208 - 6218
  • [10] CELL-SURFACE GLYCOPROTEIN OF REACTIVE STROMAL FIBROBLASTS AS A POTENTIAL ANTIBODY TARGET IN HUMAN EPITHELIAL CANCERS
    GARINCHESA, P
    OLD, LJ
    RETTIG, WJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (18) : 7235 - 7239