Imaging of HER2 with [ 89 Zr]pertuzumab in response to T-DM1 therapy

Adriana V.F. Massicano, Supum Lee, Bryant K. Crenshaw, Tolulope A. Aweda, Retta El Sayed, Ian Super, Ron Bose, Bernadette V. Marquez-Nostra, Suzanne E. Lapi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 [ 89 Zr]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 89 Zr. Mice bearing BT-474 tumors were imaged with [ 89 Zr]pertuzumab and [ 18 F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with 89 Zr with a specific activity of 0.740 MBq/μg. Overall [ 18 F]FDG images showed poor delineation of tumors. Using [ 18 F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm 3 before treatment to 89.87 ± 66.55 mm 3 after treatment. In contrast, [ 89 Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm 3 before treatment to 78.4 ± 40.43 mm 3 after treatment). Conclusion: [ 89 Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

Original languageEnglish
Pages (from-to)209-217
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume34
Issue number4
DOIs
StatePublished - May 2019

Keywords

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

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