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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Nature Portfolio
2025-07-01
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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 |
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| 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. |
| format | Article |
| id | doaj-art-444e7543107f4980a4cde108bbaebf63 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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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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