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Abstract：
Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.
摘要：
弥漫性内源性脑桥胶质瘤（DIPG）是一种罕见的儿童恶性肿瘤，预后不良。除了外部束治疗,没有有效的治疗选择。我们做了一个飞行员,使用124I-omburtamab成像和Theranosics作为治疗方法的首次人体研究，使用局部对流增强递送（CED）技术施用放射性标记的抗体。我们报告了124I-omburtamab瘤内给药的详细药代动力学和剂量学结果。方法：45例通过CED肿瘤内接受9.0-370.7MBq的124I-omburtamab的DIPG患者在注射后4、24-48、72-96、120-144和168-240小时内接受了连续的脑和全身PET/CT成像。获得系列血液样品用于动力学分析。全身,血,病变,测量正常组织的活动，估计的动力学参数(摄取和清除半衰期)，和使用OLINDA软件程序计算的辐射吸收剂量。结果：所有患者在病灶内显示出明显的活动，并保留了几天，直到最后的成像时间点都可以检测到，在病变中的平均124I停留时间为24.9小时，剂量当量为353±181mSv/MBq。全身剂量很低，剂量当量为0.69±0.28mSv/MBq。正常器官和血液中的系统分布和活动较低。对血液的辐射剂量非常低，平均值为0.27±0.21mGy/MBq。全身清除率是单指数的，平均生物半衰期为62.7h，有效半衰期为37.9h。血液清除率是双指数的，快速α相的平均生物半衰期为22.2h，较慢的β相的平均生物半衰期为155h。结论：124I-omburtamab的肿瘤内CED是DIPG的一种新型治疗方法。它允许向DIPG病变输送高辐射剂量，具有高的病变活动和低的全身活动以及高的肿瘤与正常组织的比率，并实现了广泛的安全界限。124I-omburtamab的实际治疗给药的成像允许直接估计治疗性病变和正常组织吸收剂量。
