Synapse - Biodistribution and dosimetry of intraventricularly administered (124)I-omburtamab in patients with metastatic leptomeningeal tumors

Biodistribution and dosimetry of intraventricularly administered (124)I-omburtamab in patients with metastatic leptomeningeal tumors Journal Article

Authors:	Pandit-Taskar, N.; Zanzonico, P. B.; Kramer, K.; Grkovski, M.; Fung, E. K.; Shi, W.; Zhang, Z.; Lyashchenko, S. K.; Fung, A. M.; Pentlow, K. S.; Carrasquillo, J. A.; Lewis, J. S.; Larson, S. M.; Cheung, N. K. V.; Humm, J. L.
Article Title:	Biodistribution and dosimetry of intraventricularly administered (124)I-omburtamab in patients with metastatic leptomeningeal tumors
Abstract:	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 immunoPET 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. COPYRIGHT © 2019 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	adolescent; adult; child; clinical article; controlled study; unclassified drug; cancer patient; radiation dose; positron emission tomography; prospective study; drug distribution; cerebrospinal fluid; infant; dosimetry; blood analysis; drug blood level; tracer; cerebrospinal fluid analysis; radioimmunotherapy; pet; meningeal metastasis; central nervous system metastasis; drug cerebrospinal fluid level; intraventricular; 124i; human; male; female; priority journal; article; omburtamab; omburtamab i 124
Journal Title:	Journal of Nuclear Medicine
Volume:	60
Issue:	12
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2019-12-01
Start Page:	1794
End Page:	1801
Language:	English
DOI:	10.2967/jnumed.118.219576
PUBMED:	31405921
PROVIDER:	scopus
PMCID:	PMC6894373
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075978251&doi=10.2967%2fjnumed.118.219576&partnerID=40&md5=9aa09e2600acc2276e65256fdb246f0b
Notes:	Article -- Export Date: 2 January 2020 -- Source: Scopus