Abstract
Radiation dose estimations are key for optimizing therapies that are given intra-compartmentally. We studied the role of 124I-Omburtamab (8H9) given intraventricularly via Ommaya catheter in assessing the distribution and radiation doses prior to 131I-Omburtamab therapy in patients with metastatic leptomeningeal disease and compared it to the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and recurrent metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for 131I-Omburtamab therapy underwent immunoPET imaging with 124I-8H9 followed by 131I-8H9 antibody therapy. Patients were imaged with ~74 MBq of intraventricular 124I-Omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at ~4, 24, and 48 h post-administration. Regions of interest were drawn over different segments of the CSF compartment to obtain time-activity data 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 (+ standard deviation) absorbed dose to the CSF for 131I-8H9 of 0.62±0.40 cGy/MBq, compared to 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 improved therapeutic index to leptomeningeal disease and reducing systemic doses. PET imaging-based estimates were less variable and more reliable than CSF sample-based dosimetry. PET imaging can be useful for planning treatment dose.
- Molecular Imaging
- Radiobiology/Dosimetry
- Radionuclide Therapy
- Iodine-124
- PET
- cerebrospinal fluid
- intraventricular
- radioimmunotherapy
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.