Radiation dose estimations are key for optimizing therapies. We studied the role of ¹²⁴I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before ¹³¹I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for ¹³¹I-omburtamab therapy underwent immuno-PET imaging with ¹²⁴I-8H9 followed by ¹³¹I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular ¹²⁴I-omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at approximately 4, 24, and 48 h after administration and analyzed for dosimetry calculations. Peripheral blood and CSF samples were obtained at multiple time points for dosimetry estimation. Results: Forty-two patients with complete dosimetry and therapy data were analyzed. ¹²⁴I-omburtamab PET–based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for ¹³¹I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on ¹²⁴I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on ¹³¹I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for ¹²⁴I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for ¹³¹I-omburtamab samples. The effective whole-body radiation dose for ¹²⁴I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. Conclusion: PET imaging with ¹²⁴I-omburtamab antibody administered intraventricularly allows for noninvasive estimation of dose to CSF and normal organs. High CSF-to-blood absorbed-dose ratios are noted, allowing for an improved therapeutic index to leptomeningeal disease and reduced systemic doses. PET imaging–based estimates were less variable and more reliable than CSF sample–based dosimetry.

放射剂量估计是优化治疗方法的关键。我们研究了脑室内给予¹²⁴ I-omburtamab（8H9）在评估¹³¹ I-omburtamab治疗转移性软脑膜病患者之前的分布和放射剂量的作用，并将其与脑脊液（CSF）采样的估计值进行了比较。方法：经组织学证实为符合¹³¹ I-omburtamab治疗资格标准的中枢神经系统恶性肿瘤和转移性软脑膜瘤患者，先行¹²⁴ I-8H9免疫PET显像，然后进行¹³¹ I-8H9抗体治疗。用大约74 MBq的脑室内¹²⁴为患者成像I-omburtamab通过Ommaya水库。给药后约4、24和48小时获取全身PET图像，并进行剂量学计算分析。在多个时间点获得外周血和CSF样品以进行剂量测定。结果：分析了42例完全剂量学和治疗数据的患者。基于¹²⁴ I-omburtamab PET的放射剂量学估计显示¹³¹ I-8H9对CSF的平均（±SD）吸收剂量为0.62±0.40 cGy / MBq，而基于¹²⁴ I-omburtamab CSF样品为2.22±2.19 cGy / MBq和¹³¹ I-omburtamab CSF样品的1.53±1.37 cGy / MBq 。¹²⁴的平均血液吸收剂量为0.051±0.11 cGy / MBqI-omburtamab样品为¹³¹ I-omburtamab样品为0.07±0.04 cGy / MBq 。¹²⁴ I-omburtamab的有效全身辐射剂量为0.49±0.27 mSv / MBq。平均全身清除半衰期为44.98±16.29 h。结论：脑室内给予¹²⁴ I-omburtamab抗体的PET成像可无创估计CSF和正常器官的剂量。注意到高的CSF与血液吸收剂量之比，可以改善对脑膜神经疾病的治疗指数并降低全身剂量。与基于CSF样品的剂量测定法相比，基于PET成像的估计值变异性小且可靠性更高。