PT  - JOURNAL ARTICLE
AU  - Gary A. Ulaner
AU  - Serge K. Lyashchenko
AU  - Christopher Riedl
AU  - Shutian Ruan
AU  - Pat B. Zanzonico
AU  - Diana Lake
AU  - Komal Jhaveri
AU  - Brian Zeglis
AU  - Jason S. Lewis
AU  - Joseph A. O’Donoghue
TI  - First-in-Human Human Epidermal Growth Factor Receptor 2–Targeted Imaging Using <sup>89</sup>Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer
AID  - 10.2967/jnumed.117.202010
DP  - 2018 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 900--906
VI  - 59
IP  - 6
4099  - http://jnm.snmjournals.org/content/59/6/900.short
4100  - http://jnm.snmjournals.org/content/59/6/900.full
SO  - J Nucl Med2018 Jun 01; 59
AB  - In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of 89Zr-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 89Zr. Patients underwent 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 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 89Zr-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 the 89Zr-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 89Zr-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.