First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer

In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of Zr-89-pertuzumab PET/CT for human epidermal growth factor receptor 2 (HER2)-targeted imaging in patients with HER2-positive breast cancer. Methods: Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an institutional review board-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with Zr-89. Patients underwent PET/CT with 74 MBq of Zr-89-pertuzumab in a total antibody mass of 20-50 mg of pertuzumab. PET/CT, whole-body probe counts, and blood drawing were performed over 8 d to assess pharmacokinetics, biodistribution, and dosimetry. PET/CT images were evaluated for the ability to visualize HER2-positive metastases. Results: Six patients with HER2-positive metastatic breast cancer were enrolled and administered Zr-89-pertuzumab. No toxicities occurred. Dosimetry estimates from OLINDA demonstrated that the organs receiving the highest doses (mean +/- SD) were the liver (1.75 +/- 0.21 mGy/MBq), the kidneys (1.27 +/- 0.28 mGy/MBq), and the heart wall (1.22 +/- 0.16 mGy/MBq), with an average effective dose of 0.54 +/- 0.07 mSv/MBq. PET/CT demonstrated optimal imaging 5-8 d after administration. Zr-89-pertuzumab was able to image multiple sites of malignancy and suggested that they were HER2-positive. In 2 patients with both known HER2-positive and HER2-negative primary breast cancers and brain metastases, Zr-89-pertuzumab PET/CT suggested that the brainmetastases were HER2-positive. In 1 of the 2 patients, subsequent resection of a brain metastasis proved HER2-positive disease, confirming that the Zr-89-pertuzumab avidity was a true-positive result for HER2-positive malignancy. Conclusion: This first-in-human study demonstrated safety, dosimetry, biodistribution, and successful HER2-targeted imaging with Zr-89-pertuzumab PET/CT. Potential clinical applications include assessment of the HER2 status of lesions that may not be accessible to biopsy and assessment of HER2 heterogeneity.