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.

弥漫性内在桥脑胶质瘤（DIPG）是一种罕见的儿童恶性肿瘤，预后不良。除外照射疗法外，没有有效的治疗选择。我们进行了一项试点、首次人体研究，使用¹²⁴ I-omburtamab 成像和治疗诊断学作为治疗方法，使用局部对流增强递送 (CED) 技术来施用放射性标记抗体。我们报告了¹²⁴ I-omburtamab 瘤内给药的详细药代动力学和剂量测定结果。方法： 45 名 DIPG 患者通过 CED 瘤内注射 9.0-370.7 MBq ¹²⁴ I-omburtamab，在注射后 4、24-48、72-96 天内的 3-5 个时间点进行连续脑部和全身 PET/CT 成像、输注结束后 120-144 和 168-240 小时。获得连续血样用于动力学分析。使用 OLINDA 软件程序测量全身、血液、病变和正常组织活动，估计动力学参数（摄取和清除半衰期），并计算辐射吸收剂量。结果：所有患者均在病灶内表现出显着的活动，该活动保留了数天，并且直到成像的最后时间点都可检测到，病灶中的平均¹²⁴ I 停留时间为 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。正常器官和血液中的全身分布和活性较低。血液辐射剂量非常低，平均值为 0.27 ± 0.21 mGy/MBq。全身清除率为单指数，平均生物半衰期为 62.7 小时，有效半衰期为 37.9 小时。 血液清除率为双指数，快速 α 相的平均生物半衰期为 22.2 小时，慢速 β 相的平均生物半衰期为 155 小时。结论： ¹²⁴ I-omburtamab 瘤内 CED 是 DIPG 的一种新型治疗诊断方法。它允许向 DIPG 病灶提供高辐射剂量，具有高病灶活动性和低全身活动性以及高肿瘤与正常组织比率，并实现了广泛的安全裕度。 ¹²⁴ I-omburtamab 实际治疗给药的成像可以直接估计治疗病变和正常组织吸收的剂量。