Theranostic intratumoral convection-enhanced delivery of (124)I-omburtamab in patients with diffuse intrinsic pontine glioma: Pharmacokinetics and lesion dosimetry Journal Article

   

Authors:	Pandit-Taskar, N.; Zanzonico, P. B.; Grkovski, M.; Donzelli, M.; Vietri, S. M.; Horan, C.; Serencsits, B.; Prasad, K.; Lyashchenko, S.; Kramer, K.; Dunkel, I. J.; Souweidane, M. M.
Article Title:	Theranostic intratumoral convection-enhanced delivery of (124)I-omburtamab in patients with diffuse intrinsic pontine glioma: Pharmacokinetics and lesion dosimetry
Abstract:	Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses. © 2024 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	adolescent; child; preschool child; child, preschool; young adult; glioma; radiotherapy; diagnostic imaging; radioactive iodine; tissue distribution; iodine radioisotopes; infant; dosimetry; thermodynamics; radiometry; brain stem tumor; brain stem neoplasms; convection; convection-enhanced delivery; diffuse intrinsic pontine glioma; dipg; pontine glioma; iodine-124; humans; human; male; female; positron emission tomography-computed tomography; positron emission tomography computed tomography; 124i-omburtamab; organ-absorbed doses
Journal Title:	Journal of Nuclear Medicine
Volume:	65
Issue:	9
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2024-09-01
Start Page:	1364
End Page:	1370
Language:	English
DOI:	10.2967/jnumed.123.266365
PUBMED:	39142829
PROVIDER:	scopus
PMCID:	PMC11372263
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203303722&doi=10.2967%2fjnumed.123.266365&partnerID=40&md5=c21c38100ddaa90b400a3f884f989e74
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Neeta Pandit-Taskar -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/219157