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Research ArticleBasic Science Investigations

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3

Samantha Y.A. Terry, Marije I. Koenders, Gerben M. Franssen, Tapan K. Nayak, Anne Freimoser-Grundschober, Christian Klein, Wim J. Oyen, Otto C. Boerman and Peter Laverman
Journal of Nuclear Medicine March 2016, 57 (3) 467-472; DOI: https://doi.org/10.2967/jnumed.115.162628
Samantha Y.A. Terry
1Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
2Department of Imaging Chemistry and Biology, King's College London, London, United Kingdom
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Marije I. Koenders
3Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands
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Gerben M. Franssen
1Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Tapan K. Nayak
4Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland; and
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Anne Freimoser-Grundschober
5Roche Innovation Center Zurich, Zurich, Switzerland
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Christian Klein
5Roche Innovation Center Zurich, Zurich, Switzerland
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Wim J. Oyen
1Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Otto C. Boerman
1Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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Peter Laverman
1Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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  • FIGURE 1.
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    FIGURE 1.

    Joint uptake of tracers in untreated or etanercept-treated CIA mice at 48 h (111In-28H1, 111In-DP47GS; A and B), 24 h (111In-anti-F4/80, 111In-ratIgG2b; C and D), and 1 h after injection (111In-RGD2 with/without excess unlabeled; E and F). Data are average ± SD (n = 7–10 mice/group [A–D] or 2 mice/group [E and F], 4 joints per mouse [A, C, and E]) or individual joints (n = 14–20 mice/group, 4 joints per mouse; B, D, and F). *P ≤ 0.05. **P ≤ 0.01. ***P ≤ 0.001. RA = rheumatoid arthritis.

  • FIGURE 2.
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    FIGURE 2.

    Three-dimensional SPECT/CT scans of etanercept-treated CIA mice 48 h after injection of 111In-28H1 (A) and 111In-DP47GS (B). All images are scaled equally. (C) Quantitative analysis of SPECT images. Data are average ± SD (n = 3 mice/group, 4 joints/mouse). **P ≤ 0.01.

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    FIGURE 3.

    Three-dimensional SPECT/CT scans of etanercept-treated CIA mice 24 h after injection of 111In-anti-F4/80 (A) and 111In-ratIgG2b (B). All images are scaled equally. (C) Quantitative analysis of SPECT images. Data are average ± SD (n = 3 mice/group, 4 joints/mouse). ***P ≤ 0.001.

  • FIGURE 4.
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    FIGURE 4.

    Three-dimensional SPECT/CT scans of untreated CIA mice 1 h after injection of 111In-RGD2 (A). (B) Quantitative analysis of SPECT images of joint uptake after injection of 111In-RGD2 in untreated or treated CIA mice. Data are average ± SD (n = 1–2 mice/group, 4 joints/mouse).

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    TABLE 1

    Mean and 95% CIs of Arthritis-to-Blood Uptake Ratios from Figures 1B, 1D, and 1F

    Arthritis score111In-28H1111In-DP47GS (control)111In-anti-F4/80-A3-1111In-antiratIgG2b (control)111In-RGD2Cold excess RGD2 (control)
    05.0 (2.7–7.3)0.3 (0.3–0.4)1.8 (0.6–2.9)0.2 (0.2–0.2)3.5 (2.9–4.1)2.0 (1.2–2.8)
    0.254.8 (1.8–7.7)0.5 (0.1–0.9)1.7 (0.9–2.6)0.2 (0.1–0.3)3.9 (0.1–7.7)2.0 (−3.2–7.3)
    0.58.95.8 (−65.7–77.3)1.6No dataNo dataNo data
    0.751.20.4 (−0.2–1.0)No dataNo dataNo dataNo data
    1No data0.66.6 (−29.4–42.5)No dataNo data3.4
    1.2511.8 (−2.9–26.6)0.3 (0.2–0.5)7.1 (3.2–11.1)0.4 (0.1–0.8)No dataNo data
    1.58.3 (1.9–14.7)2.2 (−1.7–6.0)6.4 (5.3–7.5)0.5 (0.4–0.7)8.23.8 (1.8–5.8)
    1.758.4 (5.5–11.2)0.6 (0.5–0.8)7.6 (6.4–8.9)0.5 (0.4–0.5)8.13.1
    25.5 (4.7–6.4)0.7 (0.3–1.2)10.4 (7.9–13.0)0.5 (0.4–0.6)7.2 (−5.9–20.3)3.5
    • Where no CIs are shown, data are from n = 1. All values over 25 were excluded. Data in parentheses are 95% CIs.

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Journal of Nuclear Medicine: 57 (3)
Journal of Nuclear Medicine
Vol. 57, Issue 3
March 1, 2016
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Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3
Samantha Y.A. Terry, Marije I. Koenders, Gerben M. Franssen, Tapan K. Nayak, Anne Freimoser-Grundschober, Christian Klein, Wim J. Oyen, Otto C. Boerman, Peter Laverman
Journal of Nuclear Medicine Mar 2016, 57 (3) 467-472; DOI: 10.2967/jnumed.115.162628

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Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3
Samantha Y.A. Terry, Marije I. Koenders, Gerben M. Franssen, Tapan K. Nayak, Anne Freimoser-Grundschober, Christian Klein, Wim J. Oyen, Otto C. Boerman, Peter Laverman
Journal of Nuclear Medicine Mar 2016, 57 (3) 467-472; DOI: 10.2967/jnumed.115.162628
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Keywords

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