Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
Department of Radiology, Weill Cornell Medical College, New York, New York.
J Nucl Med. 2024 Sep 3;65(9):1364-1370. doi: 10.2967/jnumed.123.266365.
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 I-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 I-omburtamab. Forty-five DIPG patients who received 9.0-370.7 MBq of I-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. 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 I 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. Intratumoral CED of I-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 I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses.
弥漫内生型桥脑胶质瘤（DIPG）是一种罕见的儿童恶性肿瘤，预后较差。除了外照射治疗外，目前尚无有效的治疗方法。我们使用 I-omburtamab 成像和治疗进行了一项试点、首次人体研究，作为一种使用局部增强型脑室内输送（CED）技术给予放射性标记抗体的治疗方法。我们报告了 I-omburtamab 瘤内输送的详细药代动力学和剂量学结果。45 名接受 9.0-370.7 MBq I-omburtamab 通过 CED 瘤内给药的 DIPG 患者在注射后 4、24-48、72-96、120-144 和 168-240 小时内进行了 3-5 次脑和全身 PET/CT 成像，以评估治疗效果。在输注结束后 4、24-48、72-96、120-144 和 168-240 小时内进行了 3-5 次脑和全身 PET/CT 成像。连续采集血样进行动力学分析。测量全身、血液、病变和正常组织的活动，使用 OLINDA 软件程序估计摄取和清除半衰期等动力学参数，并计算吸收剂量。所有患者的病变内均表现出明显的活性，持续数天，并可在最后一次成像时间点检测到，病变内 I 滞留时间的平均值为 24.9 小时，剂量当量为 353±181 mSv/MBq。全身剂量较低，剂量当量为 0.69±0.28 mSv/MBq。全身分布和正常器官和血液中的活性较低。血液剂量非常低，平均为 0.27±0.21 mGy/MBq。全身清除呈单指数型，生物半衰期平均为 62.7 小时，有效半衰期为 37.9 小时。血液清除呈双指数型，快速α相的生物半衰期平均为 22.2 小时，较慢β相的生物半衰期为 155 小时。 I-omburtamab 瘤内 CED 是 DIPG 的一种新型治疗方法。它可以将高辐射剂量输送到 DIPG 病变，病变内活性高，全身活性低，肿瘤与正常组织比值高，安全性好。直接估计治疗性病变和正常组织吸收剂量。
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