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
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048196981&doi=10.2967%2fjnumed.117.202010&partnerID=40&md5=d6c902b5bbb1a175cac43f89f175c294
Notes:	Article -- Export Date: 2 July 2018 -- Source: Scopus