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Cancer Biother Radiopharm. 2019 May;34(4):209-217. doi: 10.1089/cbr.2018.2654. Epub 2019 Jan 24.

Imaging of HER2 with [89Zr]pertuzumab in Response to T-DM1 Therapy.

Author information

1
1 Department of Radiology, The University of Alabama at Birmingham, Birmingham, Alabama.
2
2 Department of Radiology and Biomedical Imaging, PET Center, Yale University, New Haven, Connecticut.
3
3 Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.

Abstract

Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [89Zr]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with 89Zr. Mice bearing BT-474 tumors were imaged with [89Zr]pertuzumab and [18F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with 89Zr with a specific activity of 0.740 MBq/μg. Overall [18F]FDG images showed poor delineation of tumors. Using [18F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm3 before treatment to 89.87 ± 66.55 mm3 after treatment. In contrast, [89Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm3 before treatment to 78.4 ± 40.43 mm3 after treatment). Conclusion: [89Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

KEYWORDS:

HER2-positive breast cancer; T-DM1 therapy; [Zr]pertuzumab; molecular imaging; radiolabeled monoclonal antibody

PMID:
30676778
DOI:
10.1089/cbr.2018.2654

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