Joseph A O'Donoghue1, Jason S Lewis2,3,4,5, Neeta Pandit-Taskar3,4,6, Stephen E Fleming3,4, Heiko Schöder3,4, Steven M Larson3,4,5,6, Volkan Beylergil3, Shutian Ruan3, Serge K Lyashchenko2,3, Pat B Zanzonico1, Wolfgang A Weber3,4,5, Jorge A Carrasquillo7,4,5,6, Yelena Y Janjigian8,9. 1. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York. 3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Radiology, Weill Cornell Medical Center, New York, New York. 5. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Center for Targeted Radioimmunotherapy and Diagnosis, Ludwig Center for Cancer Immunotherapy, New York, New York. 7. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York carrasj1@mskcc.org. 8. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; and. 9. Department of Medicine, Weill Cornell Medical Center, New York, New York.
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 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.
Trastuzumab with chemotherapy improves clinical outcomes in patients with humanepidermal 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.
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