First-in-human HER2-targeted imaging using ⁸⁹Zr-pertuzumab PET/CT: Dosimetry and clinical application in patients with breast cancer

Abstract

In this first-in-human study, we evaluate the safety and dosimetry of ⁸⁹Zr-pertuzumab PET/CT for HER2-targeted imaging in patients with HER2-postive breast cancer. Materials and Methods: Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an Institutional Review Board (IRB)-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with ⁸⁹Zr. Patients underwent ⁸⁹Zr-pertuzumab PET/CT with 74 MBq of ⁸⁹Zr-pertuzumab in a total antibody mass of 20-50 mg of pertuzumab. PET/CT, whole-body probe counts, and blood draws were performed over 8 days to assess pharmacokinetics, biodistribution, and dosimetry. PET/CT images were evaluated for ability to visualize HER2-positive metastases. Results: Six patients with HER2-positive metastatic breast cancer were enrolled and administered ⁸⁹Zr-pertuzumab. No toxicities occurred. Dosimetry estimates from Organ Level Internal Dose Assessment (OLINDA) demonstrated the organs receiving the highest doses (mGy/MBq) were liver (1.75 ± 0.21), kidneys (1.27 ± 0.28), and heart wall (1.22 ± 0.16) with an average effective dose of 0.54 ± 0.07 mSv/MBq. PET/CT demonstrated optimal imaging 5-8 days post-administration. ⁸⁹Zr-pertuzumab was able to image multiple sites of HER2-positive malignancy. In two patients with both known HER2-positive and HER2-negative primary breast cancers and brain metastases, ⁸⁹Zr-pertuzumab PET/CT was able to distinguish the brain metastases as HER2-positive. Conclusion: This first-in-human study demonstrated safety, dosimetry, biodistribution, and successful HER2-targeted imaging with ⁸⁹Zr-pertuzumab PET/CT. Potential clinical applications include assessment of HER2 status of lesions which may not be accessible to biopsy and assessment of HER2 heterogeneity.