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[89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer

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Abstract

Purpose

The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [89Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures

Twelve women with HER2-positive breast cancer underwent [89Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients. Human dosimetry was calculated using OLINDA with the adult female model.

Results

High-quality images and the greatest tumor-to-nontumor contrast were achieved with images performed 5 ± 1 day post-injection. Increased [89Zr]trastuzumab uptake was seen in at least one known lesion in ten patients. The liver was the dose-limiting organ (retention of ∼12 % of the injected dose and average dose of 1.54 mSv/MBq). The effective dose was 0.47 mSv/MBq. No adverse effects of [89Zr]trastuzumab were encountered.

Conclusion

[89Zr]trastuzumab was safe and optimally imaged at least 4 days post-injection. The liver was the dose-limiting organ.

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Acknowledgments

This work was supported by the National Cancer Institute Grant CA182945, US Department of Energy Grants DESC0008432 and DESC0012737, and the Alvin J. Siteman Cancer Center Imaging and Response Assessment Core. We thank the Washington University Isotope Production team for production of Zr-89 and the Small Animal Imaging facility for animal biodistribution studies.

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Authors and Affiliations

  1. Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Richard Laforest, Suzanne E. Lapi, Reiko Oyama, Bernadette V. Marquez-Nostra, Jennifer Burkemper & Brian D. Wright

  2. The Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Richard Laforest, Suzanne E. Lapi, Ron Bose, Barry A. Siegel & Farrokh Dehdashti

  3. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Ron Bose & Adel Tabchy

  4. Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Jennifer Frye, Sarah Frye, Barry A. Siegel & Farrokh Dehdashti

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  1. Richard Laforest
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  2. Suzanne E. Lapi
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Corresponding author

Correspondence to Richard Laforest.

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Conflict of Interest

RB is a consultant for Genentech and has received an honorarium from Genentech and Novartis.

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 Helsinki declaration and its later amendments or comparable ethical standards.

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Laforest, R., Lapi, S.E., Oyama, R. et al. [89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer. Mol Imaging Biol 18, 952–959 (2016). https://doi.org/10.1007/s11307-016-0951-z

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  • DOI: https://doi.org/10.1007/s11307-016-0951-z

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