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Quantitative [18F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer

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Abstract

Purpose

Evaluation of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer.

Procedures

Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.

Results

[18F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P < 0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P < 0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r 2 = 0.85).

Conclusions

[18F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.

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Acknowledgments

We thank the National Cancer Institute for support through U01CA174706, R01CA138599, R01 CA158079, U01CA142565, and 5T32CA093240. T.E.Y. is a CPRIT Scholar and the W.A. “Tex” Moncrief Professor of Computational Oncology at The University of Texas at Austin. We would like to thank Drs. Michael Freeman and Melinda Sanders for their help with this project.

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Authors and Affiliations

  1. Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, 1912 Speedway, Austin, TX, 78712, USA

    Anna G. Sorace & Thomas E. Yankeelov

  2. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Anum K. Syed, Stephanie L. Barnes & Thomas E. Yankeelov

  3. Institute for Computational and Engineering Sciences, The University of Texas at Austin, Austin, TX, USA

    Stephanie L. Barnes & Thomas E. Yankeelov

  4. Division of Imaging Research, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    C. Chad Quarles

  5. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA

    Violeta Sanchez

  6. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    Hakmook Kang

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  1. Anna G. Sorace
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Correspondence to Anna G. Sorace.

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Sorace, A.G., Syed, A.K., Barnes, S.L. et al. Quantitative [18F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer. Mol Imaging Biol 19, 130–137 (2017). https://doi.org/10.1007/s11307-016-0994-1

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  • DOI: https://doi.org/10.1007/s11307-016-0994-1

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