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

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

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.

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / chemistry
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Deferoxamine / analogs & derivatives
  • Deferoxamine / chemistry
  • Female
  • Humans
  • Isothiocyanates / chemistry
  • Maytansine / analogs & derivatives*
  • Maytansine / therapeutic use
  • Mice
  • Mice, Nude
  • Positron Emission Tomography Computed Tomography / methods
  • Radioisotopes / administration & dosage
  • Radioisotopes / chemistry
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / chemistry
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab / therapeutic use*
  • Treatment Outcome
  • Tumor Burden / drug effects
  • X-Ray Microtomography / methods
  • Xenograft Model Antitumor Assays
  • Zirconium / administration & dosage
  • Zirconium / chemistry

Substances

  • 4-isothiocyanatobenzyl-desferrioxamine
  • Antibodies, Monoclonal, Humanized
  • Isothiocyanates
  • Radioisotopes
  • Radiopharmaceuticals
  • Maytansine
  • Zirconium
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Deferoxamine
  • pertuzumab
  • Zirconium-89
  • Trastuzumab
  • Ado-Trastuzumab Emtansine