In 2020, over 900,000 new cases of liver cancer (Hepatocellular carcinoma - HCC), including both primary and metastatic, were reported, making it the sixth most common cancer to be diagnosed globally (Foglia et al., 2023, Liver Cancer Statistics | Cancer Research UK, n.d.). Surgical resection is usually the primary curative treatment for suitable patients. However, symptoms of liver cancer are sometimes undetectable until the disease has proceeded to intermediate or late stages, where more than 75 % of patients were diagnosed when curative treatment was no longer applicable (Bruix et al., 2016, Wong et al., 2019, Hashikin et al., 2015a, Hashikin et al., 2015b). As such, therapy has focussed on systemic treatments, external beam radiotherapy and/or palliative treatments.

Transarterial radioembolisation (TARE) is a minimally invasive method of delivering radioembolic microspheres through intra-arterial routes (Meza-Junco et al., 2012). Microspheres with diameters ranging from 20 to 60 µm are delivered through the capillaries of liver tumours to provide a localised radiation dose while preserving healthy tissues (Meza-Junco et al., 2012, Kauffman et al., 2023). TheraSphere™ (Boston Scientific Corporation, Canada) and SIR-Spheres® (SIRTex, Sydney, Australia) are currently used as radioembolic agents for hepatic radioembolisation (Kauffman et al., 2023). After intra-arterial delivery to the targeted tumour, these microspheres operate similarly to brachytherapy implants, delivering therapeutic doses of (beta) radiation in situ. These commercially available microspheres use the same radioisotope, yttrium-90 (90Y), as their therapeutic radiation source Kauffman et al., 2023, Milborne et al., 2020, Weber et al., 2022).

As the radioisotope 90Y is a pure beta emitter, verifying microsphere distribution in situ via post-procedural imaging has been challenging. The 90Y bremsstrahlung imaging method may only produce a limited spatial resolution, which can significantly decrease image quality (Tan et al., 2022). In addition, longer acquisition times due to the low true-coincidence counter rate for positron emissions may restrict the quantity accuracy of 90Y microspheres PET imaging (Pasciak et al., 2014, Kao et al., 2013). Therefore, to assess therapeutic outcomes, a lung shunting study is commonly conducted using macro-aggregated albumin (MAA) labelled with Technetium-99m (99mTc) to evaluate the distribution of the microspheres in the liver and lungs (Wong et al., 2019, Tan et al., 2022). Even though the 99mTc has been considerably precise for dosimetry purposes, combining therapeutic irradiation therapy with the capacity to provide diagnostic data concurrently at the cancer site would be highly beneficial.

A theranostic radionuclide emitting both therapeutic beta and diagnostic gamma energies would be an advancement over the pure beta emitter microspheres (Sadler et al., 2022). For example, a samarium in the form of 153Sm can be used for this purpose since it has a physical half-life of 46.3 h and a thermal neutron activation cross-section of 210 barns. It can emit beta particles with energies of 0.81 MeV (20 %), 0.71 MeV (30 %), and 0.64 MeV (50 %) (Sadler et al., 2022, Hashikin et al., 2015a, Hashikin et al., 2015b), as well as gamma photons with energies of 103 keV (28 %) (Sadler et al., 2022, Wong et al., 2019). The production of 153Sm with appropriate therapeutic action and radionuclide purity via neutron activation has previously been explored (Hashikin et al., 2015a, Hashikin et al., 2015b, Wong et al., 2019, Yeong et al., 2020, Wong et al., 2020). SmCl3 was formulated as microparticles using Amberlite™ IR-120 H+ (Hashikin et al., 2015a, Hashikin et al., 2015b) and Fractogel EMD SO3− resins as a base (Hashikin et al., 2015a, Hashikin et al., 2015b). Negatively charged acrylic microspheres labelled with 153Sm have also been explored for transarterial hepatic radioembolisation producing samarium-153 loaded resin microspheres (Wong et al., 2019). Furthermore, the use of samarium as a radiation source for other oncology treatments, such as bone cancer, has also been studied. 153Sm has been used for palliative pain therapy for bone metastases in the form of samarium lexidronam (Anderson and Nunez, 2007). Ceramic seeds containing 153Sm have also been developed by incorporating Sm2O3 into SiO2 and CaO using a sol–gel processing method, resulting in a cylindrical-shaped seed 0.75 mm in diameter and 1.6 mm in length (Valente et al., 2011), as an implant to treat bone metastases. Each of these brachytherapy products utilised different samarium-based 152Sm to be activated into 153Sm prior to administration. In addition, with the existence of radiovertebroplasty therapy, combining radioactivity with bone cement for treating spinal metastases (Donanzam et al., 2013), finding the optimum matrix that could locally deliver samarium into the tumour area would also be hugely beneficial.

Despite ongoing efforts to use samarium-based brachytherapy products, geometry, size, uniformity, distribution and limited concentration of samarium in the matrices used have thus far limited their development. For example, spherical-shaped products show better uniformity in size and shape as well as greater surface area and flow properties when compared to irregular-shaped particles (Islam et al., 2017, Hossain et al., 2018). Further, achieving higher radionuclide content in the product may also allow for increased radiation to be delivered to the target site via a reduced quantity of materials used and a potential reduction in neutron activation durations (d’Abadie et al., 2021).

Several materials, including resins, polymers, albumins and liposomes, have been investigated as radioisotope delivery systems (Peltek et al., 2019). However, these bases may cause radioisotope leakage and early release, potentially migrating and thus irradiating healthy cells away from the intended tumour site of interest (Knapp and Dash, 2016, Sofou, 2008). Glasses have very high resistance to radiation and are generally non-toxic (Milborne et al., 2020). Successful use of glasses as radioisotope carrier matrices has been shown in TheraSphere™, based on a silicate glass matrix (Kauffman et al., 2023, Milborne et al., 2020). Some studies (Nijsen et al., 1999, Sharifi et al., 2022) have suggested that glasses are ineffective for in situ radiotherapy due to their density, which may impact their mobility in arteries. However, the density problem could be overcome by controlling the microsphere sizes and structures.

Phosphate-based glasses (PBGs) are unique bioresorbable glasses with great potential for internal radiation delivery due to their tailorable formulations, which control their physical, chemical, bioactivity and dissolution properties to suit the intended application (Islam et al., 2017, Hossain et al., 2018). PBGs also have relatively low melting temperatures, enabling glass preparation and various post-processing techniques to form unique geometries, including microspheres, fibres, discs and microtubes (Ahmed et al., 2019).

This study developed samarium oxide-doped PBG microspheres for potential applications in delivering radiotherapy via hepatic radioembolisation, overcoming the limitations of 90Y microspheres highlighted above. The manufacture of PBG formulations and processing into microspheres using flame spheroidisation, physicochemical characteristics (SEM, EDX, XRD), stability and radioactivity profiles are also characterised and discussed in this study. Since PBGs as the matrix can be formulated to have a similar composition to the bone, the microspheres produced could also feasibly be employed for radiovertebroplasty therapy.