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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 most patients develop progression. To our knowledge, this is the first report evaluating 89Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry 89Zr-trastuzumab. 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 half-life T1/2β was 111 h (range, 78–193 h). The median biologic whole-body retention half-life was 370 h (range, 257–578 h). PET images showed optimal tumor visualization at 5–8 d after injection. The maximum tumor SUV ranged from no to minimal uptake in 3 patients to a median of 6.8 (range, 2.9–22.7) for 20 lesions in 7 patients. Dosimetry estimates from OLINDA showed that the organs receiving the highest absorbed doses were the 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 d after injection.
O’Donoghue et al. (Wed,) studied this question.