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.

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