Quantitative [18F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer
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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.
Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.
[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).
[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.
Key wordsFMISO Oxygenation Vascular maturation Herceptin BT474 Pimonidazole Misonidazole
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.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 10.Weber DC, Tille JC, Combescure C et al (2012) The prognostic value of expression of HIF1alpha, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy. Radiat Oncol 7:66CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Society AC (2016) Cancer facts & figures 2016. American Cancer Society, AtlantaGoogle Scholar
- 22.Cho H, Ackerstaff E, Carlin S et al (2009) Noninvasive multimodality imaging of the tumor microenvironment: registered dynamic magnetic resonance imaging and positron emission tomography studies of a preclinical tumor model of tumor hypoxia. Neoplasia 11:247–259, 242p following 259 CrossRefPubMedPubMedCentralGoogle Scholar