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Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Background

Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.

Methods

Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1–5 days post administration of Z-endoxifen.

Results

Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.

Conclusion

F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

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Authors and Affiliations

  1. Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD, USA

    Frank I. Lin & P. M. Jacobs

  2. Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA

    Frank I. Lin, E. M. Gonzalez, K. A. Kurdziel, A. Ton, B. Turkbey, P. L. Choyke & M. L. Lindenberg

  3. Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    S. Kummar, K. Do, J. M. Collins & J. H. Doroshow

  4. Biometric Research Program, National Cancer Institute, NIH, Bethesda, MD, USA

    J. Shih

  5. Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, 21702, USA

    S. Adler

  6. Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA

    S. Bhattacharyya

  7. Early Clinical Trials Development Program, DCTD, National Cancer Institute, Bethesda, MD, USA

    A. P. Chen

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  1. Frank I. Lin
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Correspondence to Frank I. Lin.

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Funding

This project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

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All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the NIH/NCI IRB.

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Informed consent was obtained from all individual participants included in the study.

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Lin, F.I., Gonzalez, E.M., Kummar, S. et al. Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy. Eur J Nucl Med Mol Imaging 44, 500–508 (2017). https://doi.org/10.1007/s00259-016-3561-8

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  • DOI: https://doi.org/10.1007/s00259-016-3561-8

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