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

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.