Pharmacokinetics, Biodistribution, and Radiation Dosimetry for 89Zr-Trastuzumab in Patients with Esophagogastric Cancer
Pharmacokinetics, Biodistribution, and Radiation Dosimetry for 89Zr-Trastuzumab in Patients with Esophagogastric Cancer
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DOI：
10.2967/jnumed.117.194555
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发表时间：
2018-01-01
影响因子：
9.3
通讯作者：
Janjigian, Yelena Y.
中科院分区：
文献类型：
--
作者：
O'Donoghue, Joseph A.;Lewis, Jason S.;Janjigian, Yelena Y.
曲妥珠单抗联合化疗可改善人表皮生长因子受体2 （HER2）阳性食管胃腺癌（EGA）患者的临床预后。尽管有治疗效果，但反应很少完全，大多数患者会出现进展。据我们所知，这是第一份评估zr -89-曲妥珠单抗治疗her2阳性EGA的报告；在这里，我们评估了zr -89-曲妥珠单抗的安全性、药代动力学、生物分布和剂量学。方法：曲妥珠单抗与去铁胺结合，并用Zr-89进行放射性标记。10例转移性her2阳性EGA患者的平均活度为184 MBq。PET成像、全身探针计数和抽血评估药代动力学、生物分布和剂量学。结果：未观察到明显的临床毒性。在输注结束时，估计的zr -89-曲妥珠单抗血浆体积中位数为注射剂量的102%（范围，78%-113%）。中位生物半衰期T-1/2 β为111小时（范围78-193小时）。中位生物全身保留半衰期为370小时（范围为257-578小时）。PET图像显示注射后5-8 d肿瘤显示最佳。3例患者的最大肿瘤SUV从无摄取到最小摄取，7例患者的20个病变的中位SUV为6.8（范围，2.9-22.7）。OLINDA的剂量学估计显示，接受最高吸收剂量的器官是肝脏和心脏壁，中位数分别为1.37和1.12 mGy/MBq。结论：zr -89-曲妥珠单抗成像示踪剂对her2阳性EGA患者是安全的，可提供高质量的图像，最佳成像时间为注射后5-8 d。
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-89-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry Zr-89-trastuzumab. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with Zr-89. 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 Zr-89-trastuzumab in plasma volume was a median 102% (range, 78%-113%) of the injected dose. The median biologic half-life T-1/2 beta 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: Zr-89-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.