Biodistribution and Dosimetry of Intraventricularly Administered I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Radiation dose estimations are key for optimizing therapies. We studied the role of I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for I-omburtamab therapy underwent immuno-PET imaging with I-8H9 followed by I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular I-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. Forty-two patients with complete dosimetry and therapy data were analyzed. I-omburtamab PET-based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for I-omburtamab samples. The effective whole-body radiation dose for I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. PET imaging with I-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.