Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York.
J Nucl Med. 2018 Jan;59(1):161-166. doi: 10.2967/jnumed.117.194555. Epub 2017 Jun 21.
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 Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry Zr-trastuzumab. Trastuzumab was conjugated with deferoxamine and radiolabeled with Zr. 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. No clinically significant toxicities were observed. At the end of infusion, the estimated Zr-trastuzumab in plasma volume was a median 102% (range, 78%-113%) of the injected dose. The median biologic half-life T 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. Zr-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.
曲妥珠单抗联合化疗可改善人表皮生长因子受体 2（HER2）阳性胃食管腺癌（EGA）患者的临床结局。尽管有治疗益处，但反应很少完全，大多数患者都会出现进展。据我们所知，这是首次评估 Zr-曲妥珠单抗在 HER2 阳性 EGA 中的应用；在这里，我们评估了 Zr-曲妥珠单抗的安全性、药代动力学、生物分布和剂量学。曲妥珠单抗与去铁胺偶联并用 Zr 标记。将 184MBq 的平均活性物质施用于 10 名转移性 HER2 阳性 EGA 患者。进行 PET 成像、全身探头计数和血液采集，以评估药代动力学、生物分布和剂量学。未观察到临床显著的毒性。在输注结束时，估计 Zr-曲妥珠单抗在血浆体积中的含量为注射剂量的中位数 102%（范围 78%-113%）。中位生物学半衰期 T 为 111h（范围 78-193h）。中位生物学全身保留半衰期为 370h（范围 257-578h）。PET 图像显示在注射后 5-8d 时肿瘤可视化最佳。3 名患者的最大肿瘤 SUV 为无摄取至最小摄取，7 名患者 20 个病灶中的中位数为 6.8（范围 2.9-22.7）。OLINDA 的剂量学估计显示，肝脏和心脏壁吸收剂量最高的器官，中位数分别为 1.37 和 1.12mGy/MBq。Zr-曲妥珠单抗显像示踪剂在 HER2 阳性 EGA 患者中是安全的，并提供高质量的图像，最佳成像时间为注射后 5-8d。
