Design and optimization of imageable microspheres for locoregional cancer therapy

Abstract Transarterial radioembolization (TARE) is an increasingly important technique for treating liver-based malignancies. Personalized treatment planning and dosimetry are not yet possible due to poor imageability of existing TARE agents. This study presents the design and development of a cohor...

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Main Authors: Brenna Kettlewell, Andrea Armstrong, Kirill Levin, Riad Salem, Edward Kim, Robert J. Lewandowski, Alexander Loizides, Robert J. Abraham, Daniel Boyd
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12182-5
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author Brenna Kettlewell
Andrea Armstrong
Kirill Levin
Riad Salem
Edward Kim
Robert J. Lewandowski
Alexander Loizides
Robert J. Abraham
Daniel Boyd
author_facet Brenna Kettlewell
Andrea Armstrong
Kirill Levin
Riad Salem
Edward Kim
Robert J. Lewandowski
Alexander Loizides
Robert J. Abraham
Daniel Boyd
author_sort Brenna Kettlewell
collection DOAJ
description Abstract Transarterial radioembolization (TARE) is an increasingly important technique for treating liver-based malignancies. Personalized treatment planning and dosimetry are not yet possible due to poor imageability of existing TARE agents. This study presents the design and development of a cohort of imageable glass microspheres that are compatible with readily available imaging equipment, including single-photon emission computed tomography (SPECT) and computed tomography (CT). A statistical modelling approach was used to investigate how the addition of holmium (Ho), a high atomic number and high k-edge element, to a Y2O3-Al2O3-SiO2 (YAS) glass matrix impacts material properties such as density, CT imageability, and glass transition temperature (Tg). The microspheres demonstrated excellent radiopacity, with Hounsfield Unit (HU) values ranging up to ~ 19,800 at 70 kVp, high thermal stability, exhibiting Tg values up to 895 °C, no cytotoxic potential, and negligible ion leaching pre- and post-irradiation to 2600 GBq/g Ho-166, supporting their safety and efficacy for locoregional therapies. Statistical modelling elucidated how the fraction of holmium oxide content within the glass matrix impacts density, CT imageability, and Tg. The ability to visualize the microspheres intra- and post-operatively via CT and SPECT imaging, combined with stable radionuclide incorporation and high achievable specific activity, marks a significant advancement in TARE, and represents an opportunity to expand applicability to cancers beyond the liver.
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spelling doaj-art-444e7543107f4980a4cde108bbaebf632025-08-20T03:42:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-12182-5Design and optimization of imageable microspheres for locoregional cancer therapyBrenna Kettlewell0Andrea Armstrong1Kirill Levin2Riad Salem3Edward Kim4Robert J. Lewandowski5Alexander Loizides6Robert J. Abraham7Daniel Boyd8School of Biomedical Engineering, Dalhousie UniversitySynergy Oncology Inc.Department of Chemistry and Biochemistry, McGill UniversityDepartment of Radiology, Northwestern University Feinberg School of MedicineDepartment of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount SinaiDepartment of Radiology, Section of Interventional Radiology, Northwestern University Feinberg School of MedicineDepartment of Radiology, Innsbruck Medical UniversityDivision of Interventional Radiology, Department of Diagnostic Radiology, Dalhousie UniversitySchool of Biomedical Engineering, Dalhousie UniversityAbstract Transarterial radioembolization (TARE) is an increasingly important technique for treating liver-based malignancies. Personalized treatment planning and dosimetry are not yet possible due to poor imageability of existing TARE agents. This study presents the design and development of a cohort of imageable glass microspheres that are compatible with readily available imaging equipment, including single-photon emission computed tomography (SPECT) and computed tomography (CT). A statistical modelling approach was used to investigate how the addition of holmium (Ho), a high atomic number and high k-edge element, to a Y2O3-Al2O3-SiO2 (YAS) glass matrix impacts material properties such as density, CT imageability, and glass transition temperature (Tg). The microspheres demonstrated excellent radiopacity, with Hounsfield Unit (HU) values ranging up to ~ 19,800 at 70 kVp, high thermal stability, exhibiting Tg values up to 895 °C, no cytotoxic potential, and negligible ion leaching pre- and post-irradiation to 2600 GBq/g Ho-166, supporting their safety and efficacy for locoregional therapies. Statistical modelling elucidated how the fraction of holmium oxide content within the glass matrix impacts density, CT imageability, and Tg. The ability to visualize the microspheres intra- and post-operatively via CT and SPECT imaging, combined with stable radionuclide incorporation and high achievable specific activity, marks a significant advancement in TARE, and represents an opportunity to expand applicability to cancers beyond the liver.https://doi.org/10.1038/s41598-025-12182-5Radionuclide TherapyRadioembolizationOncologyHolmium-166GlassTheranostic
spellingShingle Brenna Kettlewell
Andrea Armstrong
Kirill Levin
Riad Salem
Edward Kim
Robert J. Lewandowski
Alexander Loizides
Robert J. Abraham
Daniel Boyd
Design and optimization of imageable microspheres for locoregional cancer therapy
Scientific Reports
Radionuclide Therapy
Radioembolization
Oncology
Holmium-166
Glass
Theranostic
title Design and optimization of imageable microspheres for locoregional cancer therapy
title_full Design and optimization of imageable microspheres for locoregional cancer therapy
title_fullStr Design and optimization of imageable microspheres for locoregional cancer therapy
title_full_unstemmed Design and optimization of imageable microspheres for locoregional cancer therapy
title_short Design and optimization of imageable microspheres for locoregional cancer therapy
title_sort design and optimization of imageable microspheres for locoregional cancer therapy
topic Radionuclide Therapy
Radioembolization
Oncology
Holmium-166
Glass
Theranostic
url https://doi.org/10.1038/s41598-025-12182-5
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