Kettlewell Brenna, Armstrong Andrea, Levin Kirill, Salem Riad, Kim Edward, Lewandowski Robert J, Loizides Alexander, Abraham Robert J, Boyd Daniel
School of Biomedical Engineering, Dalhousie University, 5199 University Avenue, PO BOX 15000, Halifax, NS, B3H 4R2, Canada.
Synergy Oncology Inc., Halifax, NS, Canada.
Sci Rep. 2025 Jul 28;15(1):27487. doi: 10.1038/s41598-025-12182-5.
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 YO-AlO-SiO (YAS) glass matrix impacts material properties such as density, CT imageability, and glass transition temperature (T). The microspheres demonstrated excellent radiopacity, with Hounsfield Unit (HU) values ranging up to ~ 19,800 at 70 kVp, high thermal stability, exhibiting T 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 T. 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.
经动脉放射性栓塞术（TARE）是一种治疗肝脏恶性肿瘤日益重要的技术。由于现有TARE剂的成像性较差，个性化治疗计划和剂量测定尚无法实现。本研究介绍了一组可成像玻璃微球的设计与开发，这些微球与包括单光子发射计算机断层扫描（SPECT）和计算机断层扫描（CT）在内的现有成像设备兼容。采用统计建模方法研究了向YO-AlO-SiO（YAS）玻璃基质中添加钬（Ho，一种高原子序数和高k边元素）如何影响诸如密度、CT成像性和玻璃化转变温度（T）等材料特性。这些微球显示出优异的射线不透性，在70 kVp时亨氏单位（HU）值高达约19800，具有高热稳定性，T值高达895°C，无细胞毒性潜力，在辐照至2600 GBq/g Ho-166前后离子浸出可忽略不计，支持其在局部区域治疗中的安全性和有效性。统计建模阐明了玻璃基质中氧化钬含量的比例如何影响密度、CT成像性和T。通过CT和SPECT成像在术中及术后可视化微球的能力，结合稳定的放射性核素掺入和高可实现的比活度，标志着TARE的重大进展，并代表了将适用性扩展至肝脏以外癌症的机会。
