Biodistribution of 89Zr-trastuzumab and PET Imaging of HER2-Positive Lesions in Patients With Metastatic Breast Cancer

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Abstract
We performed a feasibility study to determine the optimal dosage and time of administration of the monoclonal antibody zirconium‐89 (89Zr)‐trastuzumab to enable positron emission tomography (PET) imaging of human epidermal growth factor receptor 2 (HER2)‐positive lesions. Fourteen patients with HER2‐positive metastatic breast cancer received 37 MBq of 89Zr‐trastuzumab at one of three doses (10 or 50 mg for those who were trastuzumab‐naive and 10 mg for those who were already on trastuzumab treatment). The patients underwent at least two PET scans between days 2 and 5. The results of the study showed that the best time for assessment of 89Zr‐trastuzumab uptake by tumors was 4–5 days after the injection. For optimal PET‐scan results, trastuzumab‐naive patients required a 50 mg dose of 89Zr‐trastuzumab, and patients already on trastuzumab treatment required a 10 mg dose. The accumulation of 89Zr‐trastuzumab in lesions allowed PET imaging of most of the known lesions and some that had been undetected earlier. The relative uptake values (RUVs) (mean ± SEM) were 12.8 ± 5.8, 4.1 ± 1.6, and 3.5 ± 4.2 in liver, bone, and brain lesions, respectively, and 5.9 ± 2.4, 2.8 ± 0.7, 4.0 ± 0.7, and 0.20 ± 0.1 in normal liver, spleen, kidneys, and brain tissue, respectively. PET scanning after administration of 89Zr‐trastuzumab at appropriate doses allows visualization and quantification of uptake in HER2‐positive lesions in patients with metastatic breast cancer. Clinical Pharmacology & Therapeutics (2010) 87 5, 586–592. doi: 10.1038/clpt.2010.12