PT - JOURNAL ARTICLE AU - Neeta Pandit-Taskar AU - Pat B. Zanzonico AU - Kim Kramer AU - Milan Grkovski AU - Edward K. Fung AU - Weiji Shi AU - Zhigang Zhang AU - Serge K. Lyashchenko AU - Alex M. Fung AU - Keith S. Pentlow AU - Jorge A. Carrasquillo AU - Jason S. Lewis AU - Steven M. Larson AU - Nai-Kong V. Cheung AU - John L. Humm TI - Biodistribution and Dosimetry of Intraventricularly Administered <sup>124</sup>I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors AID - 10.2967/jnumed.118.219576 DP - 2019 Dec 01 TA - Journal of Nuclear Medicine PG - 1794--1801 VI - 60 IP - 12 4099 - http://jnm.snmjournals.org/content/60/12/1794.short 4100 - http://jnm.snmjournals.org/content/60/12/1794.full SO - J Nucl Med2019 Dec 01; 60 AB - 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.