Abstract
Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete and the majority of patients develop progression. This is the first report evaluating 89Zr-trastuzumab in HER2-positive EGA in which we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with 89Zr. A mean activity of 184 MBq was administered to 10 patients with metastatic HER2-positive EGA. PET imaging, whole-body probe counts, and blood draws were performed to assess pharmacokinetics, biodistribution and dosimetry. Results: No clinically significant toxicities were observed. At the end of infusion, the estimated 89Zr-trastuzumab in plasma volume was a median 102% (range 78-113%) of the injected dose. The median biologic T1/2 β was 111 h (range 78-193 h). Median biologic whole-body retention half-life was 370 h (range 257-578 h). PET images showed optimal tumor visualization at 5-8 days post-injection. The maximum tumor standard uptake value (SUV) ranged from no to minimal uptake in three patients to a median of 6.8 (range 2.9-22.7) for 20 lesions in seven patients. Dosimetry estimates from Organ Level Internal Dose Assessment (OLINDA) showed that the organs receiving the highest absorbed doses were liver and heart wall with median values of 1.37 and 1.12 mGy/MBq, respectively. Conclusion: 89Zr-trastuzumab imaging tracer is safe and provides high-quality images in patients with HER2-positive EGA, with an optimal imaging time of 5-8 days post-injection.
- Monoclonal Antibodies
- Oncology: GI
- Radioimmunoimaging
- 89Zr
- HER2
- esophageal cancer
- gastric cancer
- trastuzumab
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.