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Research ArticleBasic Science Investigations

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

Alison E. John, Jeni C. Luckett, Amanda L. Tatler, Ramla O. Awais, Ami Desai, Anthony Habgood, Steve Ludbrook, Andy D. Blanchard, Alan C. Perkins, R. Gisli Jenkins and John F. Marshall
Journal of Nuclear Medicine December 2013, 54 (12) 2146-2152; DOI: https://doi.org/10.2967/jnumed.113.120592
Alison E. John
1Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom
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Jeni C. Luckett
2Centre for Biomolecular Sciences, University of Nottingham, Nottingham, United Kingdom
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Amanda L. Tatler
1Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom
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Ramla O. Awais
3Radiological and Imaging Sciences, University of Nottingham, Nottingham, United Kingdom
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Ami Desai
4Institute of Cancer, Queen Mary, University of London, London, United Kingdom; and
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Anthony Habgood
1Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom
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Steve Ludbrook
5GlaxoSmithKline, Stevenage, United Kingdom
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Andy D. Blanchard
5GlaxoSmithKline, Stevenage, United Kingdom
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Alan C. Perkins
3Radiological and Imaging Sciences, University of Nottingham, Nottingham, United Kingdom
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R. Gisli Jenkins
1Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom
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John F. Marshall
4Institute of Cancer, Queen Mary, University of London, London, United Kingdom; and
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  • FIGURE 1.
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    FIGURE 1.

    Binding of 111In-DTPA-A20FMDV2 peptide in lungs of fibrotic mice was detected at low level in lungs of saline-treated mice (A) with no evidence of parenchymal damage on the corresponding CT scans (C). Level of 111In- DTPA-A20FMDV2 binding was greatly increased in bleomycin-treated animals (B), which showed clear evidence of parenchymal damage in axial CT scans (D).

  • FIGURE 2.
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    FIGURE 2.

    Levels of binding in lungs, expressed as percentage of initial activity of 111In-labeled peptide, were compared in bleomycin- (n = 18) and saline- (n = 8) treated mice. Binding of 111In-DTPA-A20FMDVran peptide in lungs of saline- (n = 6) or bleomycin- (n = 8) treated mice was also assessed. Data are presented as mean ± SEM. ****P < 0.0001. **P < 0.01.

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    FIGURE 3.

    Axial SPECT/CT scans of thorax detected binding of 111In-DTPA-A20FMDV2 in lungs of bleomycin-treated animals receiving αvβ6-blocking antibody (A) or IgG2a isotype control (B) (2.5 mg/kg) 24 h before imaging. Effect of αvβ6-blocking (C) and IgG2a isotype control (D) antibodies on binding of 111In-DTPA-A20FMDV2 was also assessed in saline-treated mice.

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    FIGURE 4.

    Levels of binding in lungs, expressed as percentage of initial activity of 111In-labeled peptide were quantified in saline- (n = 6) or bleomycin- (n = 5) treated animals pretreated with αvβ6-blocking antibody or mice pretreated with IgG2a isotype control (n = 4/group). Data are presented as mean ± SEM. *P < 0.05. ****P < 0.0001.

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    FIGURE 5.

    Binding of 111In-DTPA-A20FMDV2 to αvβ6 integrins was assessed in lungs of bleomycin-instilled mice (n = 6/group) and saline-treated mice (n = 4/group), and levels of peptide binding were compared after repeated scans at 2 and 4 wk after administration.

  • FIGURE 6.
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    FIGURE 6.

    Correlation of 111In-DTPA-A20FMDV2 binding within lungs at 28 d after saline (white circles; n = 3) or bleomycin (black circles; n = 3) with epithelial αvβ6 expression in lungs (A). Correlation of 111In-DTPA-A20FMDV2 binding at day 28 (B) and day 14 (C) after saline (n = 4) or bleomycin (n = 6) treatment with lung hydroxyproline levels on day 28.

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Journal of Nuclear Medicine: 54 (12)
Journal of Nuclear Medicine
Vol. 54, Issue 12
December 1, 2013
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Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis
Alison E. John, Jeni C. Luckett, Amanda L. Tatler, Ramla O. Awais, Ami Desai, Anthony Habgood, Steve Ludbrook, Andy D. Blanchard, Alan C. Perkins, R. Gisli Jenkins, John F. Marshall
Journal of Nuclear Medicine Dec 2013, 54 (12) 2146-2152; DOI: 10.2967/jnumed.113.120592

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Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis
Alison E. John, Jeni C. Luckett, Amanda L. Tatler, Ramla O. Awais, Ami Desai, Anthony Habgood, Steve Ludbrook, Andy D. Blanchard, Alan C. Perkins, R. Gisli Jenkins, John F. Marshall
Journal of Nuclear Medicine Dec 2013, 54 (12) 2146-2152; DOI: 10.2967/jnumed.113.120592
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Keywords

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