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Utility of [18 F]FLT-PET to Assess Treatment Response in Trastuzumab-Resistant and Trastuzumab-Sensitive HER2-Overexpressing Human Breast Cancer Xenografts

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Abstract

Purpose

The objective of this study was to evaluate 3’-deoxy-3’-[18 F]fluorothymidine ([18 F]FLT) positron emission tomography (PET) as an early marker of trastuzumab response in HER2-overexpressing xenografts.

Procedures

Tumor-to-muscle ratios were compared between both trastuzumab-sensitive and trastuzumab-resistant cohorts prior to and after one and two treatments.

Results

A significant difference (P = 0.03) was observed between treated and control trastuzumab-sensitive xenografts after one treatment, which preceded between-group differences in tumor volume. Reduced Ki67 (P = 0.02) and thymidine kinase 1 (TK1) (P = 0.35) immunoreactivity was observed in the treated xenografts. No significant differences in volume, tumor-to-muscle ratio, or immunoreactivity were observed between treated and control trastuzumab-resistant cohorts. A significant difference (P = 0.02) in tumor-to-muscle ratio was observed between trastuzumab-sensitive and trastuzumab-resistant cohorts after two treatments; however, tumor volumes were also different (P = 0.04). Ki67 (P = 0.04) and TK1 (P = 0.24) immunoreactivity was ~50 % less in trastuzumab-sensitive xenografts.

Conclusions

[18 F]FLT-PET provided early response assessment in trastuzumab-sensitive xenografts but only differentiated between trastuzumab-resistant and trastuzumab-sensitive xenografts concurrent with differences in tumor size.

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Acknowledgments

We thank the National Institutes of Health for funding through R01 CA138599, R01 CA80195, Vanderbilt Breast Cancer SPORE P50 CA98131, and Vanderbilt-Ingram Cancer Center Support Grant P30 CA68485, U24 CA126588, P50 CA12832, and 1 S10 RR17858. We would like to thank Dr. Noor Tantawy and George Wilson for imaging assistance; Dr. Joseph Roland (Vanderbilt University Epithelial Biology Center Core) and Dr. Anna Sorace with immunohistochemistry data analysis; Jarrod True, Dr. Zoe Yu, M.D., and Carlo Malabanon (Vanderbilt University MMPC) for animal care assistance; and Cammie Rinehart Sutton for cell culture and assistance with mouse studies.

Conflict of interest

T.E.Y. was a consultant for Eli Lilly and Company within the last 36 months.

Author information

Authors and Affiliations

  1. Institute of Imaging Science, Vanderbilt University, 1161 21st Ave. South, MCN AA-1105, Nashville, TN, 37232-2675, USA

    Jennifer G. Whisenant, J. Oliver McIntyre, Todd E. Peterson, H. Charles Manning & Thomas E. Yankeelov

  2. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Jennifer G. Whisenant, J. Oliver McIntyre, Todd E. Peterson, H. Charles Manning & Thomas E. Yankeelov

  3. Department of Cancer Biology, Vanderbilt University, Nashville, TN, 37232-2675, USA

    J. Oliver McIntyre, Carlos L. Arteaga & Thomas E. Yankeelov

  4. Department of Physics, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Todd E. Peterson & Thomas E. Yankeelov

  5. Department of Biostatistics, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Hakmook Kang

  6. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232-2675, USA

    H. Charles Manning & Thomas E. Yankeelov

  7. Department of Neurological Surgery, Vanderbilt University, Nashville, TN, 37232-2675, USA

    H. Charles Manning

  8. Department of Medicine, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Carlos L. Arteaga

  9. Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Carlos L. Arteaga

  10. Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232-2675, USA

    Violeta Sánchez, H. Charles Manning & Thomas E. Yankeelov

Authors
  1. Jennifer G. Whisenant
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  2. J. Oliver McIntyre
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  3. Todd E. Peterson
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  6. H. Charles Manning
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Correspondence to Thomas E. Yankeelov.

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Whisenant, J.G., McIntyre, J.O., Peterson, T.E. et al. Utility of [18 F]FLT-PET to Assess Treatment Response in Trastuzumab-Resistant and Trastuzumab-Sensitive HER2-Overexpressing Human Breast Cancer Xenografts. Mol Imaging Biol 17, 119–128 (2015). https://doi.org/10.1007/s11307-014-0770-z

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  • DOI: https://doi.org/10.1007/s11307-014-0770-z

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