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FDG-PET as a pharmacodynamic biomarker for early assessment of treatment response to linifanib (ABT-869) in a non-small cell lung cancer xenograft model

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Abstract

Linifanib (ABT-869) is a multitargeted receptor tyrosine kinase inhibitor. This work aims to evaluate F-fluorodeoxyglucose-positron emission tomography (FDG-PET) as a pharmacodynamic (PD) biomarker for linifanib treatment utilizing the Calu-6 model of human non-small cell lung (NSCLC) cancer in SCID-beige mice. Animals received either vehicle or 12.5 mg/kg linifanib orally twice a day for the duration of the study. Imaging was performed at −1, 1, 3, and 7 days after beginning treatment (n = 12–14 per group). Linifanib inhibited tumor growth and suppressed tumor metabolic activity. Changes in tumor FDG uptake were observed as early as 1 day after beginning linifanib treatment and were sustained for the duration of the study. This study confirms that linifanib is efficacious in this xenograft model of human NSCLC and confirms FDG-PET is a potential PD biomarker strategy for linifanib therapy.

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Acknowledgments

The authors would like to thank Alan Fan for critical reading of the manuscript.

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Authors and Affiliations

  1. Advanced Technology Translational Sciences, Global Pharmaceutical R & D, Abbott Laboratories, Abbott Park, IL, 60064, USA

    Sarah R. Mudd, Martin J. Voorbach, Gerard B. Fox, Yanping Luo & Mark Day

  2. Cancer Research, Global Pharmaceutical R & D, Abbott Laboratories, Abbott Park, IL, 60064, USA

    David R. Reuter, Paul Tapang, Jonathan A. Hickson, Marion Refici-Buhr & Daniel H. Albert

  3. Department R4DF, AP4A-1, 100 Abbott Park Road, Abbott Park, IL, 60064, USA

    Sarah R. Mudd

Authors
  1. Sarah R. Mudd
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  2. Martin J. Voorbach
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  3. David R. Reuter
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  4. Paul Tapang
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  5. Jonathan A. Hickson
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  6. Marion Refici-Buhr
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  7. Gerard B. Fox
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  8. Daniel H. Albert
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  9. Yanping Luo
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  10. Mark Day
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Corresponding author

Correspondence to Sarah R. Mudd.

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Disclaimer: Authors are current or previous employees of and currently own stock and/or stock options in Abbott Laboratories.

Sarah R. Mudd and Martin J. Voorbach have contributed equally to this work.

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Mudd, S.R., Voorbach, M.J., Reuter, D.R. et al. FDG-PET as a pharmacodynamic biomarker for early assessment of treatment response to linifanib (ABT-869) in a non-small cell lung cancer xenograft model. Cancer Chemother Pharmacol 69, 1669–1672 (2012). https://doi.org/10.1007/s00280-012-1840-z

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  • DOI: https://doi.org/10.1007/s00280-012-1840-z

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