First-in-human human epidermal growth factor receptor 2-targeted imaging using (89)Zr-Pertuzumab PET/CT: Dosimetry and clinical application in patients with breast cancer Journal Article

Authors: Ulaner, G. A.; Lyashchenko, S. K.; Riedl, C.; Ruan, S.; Zanzonico, P. B.; Lake, D.; Jhaveri, K.; Zeglis, B.; Lewis, J. S.; O'Donoghue, J. A.
Article Title: First-in-human human epidermal growth factor receptor 2-targeted imaging using (89)Zr-Pertuzumab PET/CT: Dosimetry and clinical application in patients with breast cancer
Abstract: In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of89Zr-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. Pertuzu-mab was conjugated with deferoxamine and radiolabeled with89Zr. Patients underwent PET/CT with 74 MBq of89Zr-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 administered89Zr-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.89Zr-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,89Zr-pertuzumab PET/CT suggested that the brain metastases were HER2-positive. In 1 of the 2 patients, subsequent resection of a brain metastasis proved HER2-positive disease, confirming that the89Zr-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 with89Zr-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. COPYRIGHT © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords: breast cancer; oncology; dosimetry; pet/ct; radiobiology; 89zr-pertuzumab
Journal Title: Journal of Nuclear Medicine
Volume: 59
Issue: 6
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2018-06-01
Start Page: 900
End Page: 906
Language: English
DOI: 10.2967/jnumed.117.202010
PROVIDER: scopus
PMCID: PMC6004559
PUBMED: 29146695
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Christopher Riedl
    51 Riedl
  2. Gary Ulaner
    120 Ulaner
  3. Diana E Lake
    78 Lake
  4. Komal Lachhman Jhaveri
    78 Jhaveri
  5. Pat B Zanzonico
    281 Zanzonico
  6. Shutian Ruan
    50 Ruan
  7. Jason S Lewis
    307 Lewis