Arjuna, Andi
(2025)
Development of samarium-doped microspheres for internal radiotherapy treatment of bone metastases.
PhD thesis, University of Nottingham.
Abstract
Internal radiotherapy, also known as brachytherapy, and or selective internal radiotherapy (SIRT), delivers radioactive sources inside the body, near to or into malignant tumours, which may be particularly effective when malignancies are not responding to external beam radiotherapy. 90Y is currently used for internal radiotherapy and commercially available products approved by the FDA. However, the 90Y contained in these yttrium-doped microspheres are pure beta emitters only, which generally needs additional radioactive 99mTc (technetium) for dose calculation and cancer detection in pre-treatments and for dose monitoring and distribution in post treatments.
Thus, developing theranostic radionuclide-based microspheres containing both a therapeutic beta and diagnostic gamma emitter would be a significant advancement over pure beta emitter microspheres. Therefore, this study aimed to develop samarium-doped microspheres using phosphate-based glass and poly(lactic acid) as the matrix, processed through a flame spheroidisation process, which could potentially be used for internal radiotherapy applications.
A novel processing, flame spheroidisation, method developed in our group was used to simply modify the ratio of phosphate-based glass (as the matrix) to samarium oxide (as the radionuclide source) to form samarium-doped solid microspheres. This study investigated the production of high concentrations of samarium-content doped phosphate-based glass microspheres. Uniform microspheres with significantly high samarium content of up to 44 %mol in P60 glass doped with samarium (1:3) were produced. The samarium-doped microspheres appeared to be glass–ceramic. After 15 min of neutron activation (neutron flux 3.01 × 1013 n.cm2.s1), the specific activity of the microspheres (3:1, 1:1, 1:3 of P60 glass:samarium oxide) was 0.28, 0.54 and 0.58 GBq.g-1, respectively. Therefore, the samarium solid microspheres produced in this study provide great potential for improving internal radiotherapy treatment for liver cancer by avoiding complex procedures and using fewer microspheres with shorter irradiation time.
Further development of samarium microspheres was achieved by modifying the microspheres into samarium-P40 porous microspheres. Samarium oxide was mixed with P40 as the matrix and processed through our flame spheroidisation method with the help of CaCO3 as porogen. A glass-ceramic structure porous samarium-P40 was successfully produced, within a specific crystalline phase identified to be samarium oxide. Within 5 hours irradiation time the radioactivity of 153Sm from samarium-P40 porous microspheres reached ~4 GBq/g in P40:Sm(3:1) microspheres.
The production of samarium-doped PLA microspheres was also studied, where the samarium oxide was mixed with PLA powder, and processed in flame spheroidisation. This pioneering study proved that flame spheroidisation was a rapid, simple and effective process for producing radionuclide-polymeric microspheres. The Sm-PLA microspheres were durable during the 28-day degradation study, without any significant changes in PLA structure after a high level of samarium doping and spheroidisation process. The radioactivity of 153Sm from samarium-PLA microspheres obtained specific activity around 7.76 GBq/g, after 3 hours of irradiation time.
The achievements to have a range of radioactivity in all samarium-doped microspheres developed, allow an efficient approach to achieve and modify the radioactive dose requirements in pre-treatments of internal radiotherapy, by simply incorporation and tailoring the level of stable 152Sm content before the flame spheroidisation process. Finally, a feasibility study to produce smaller-sized samarium-phosphate glass microspheres was also conducted, to improve and ensure that radioactive samarium (after activation) could reach the tumour tissues as delivered internally. We confirm that samarium-P40 microspheres within the size of 30 – 50 µm were successfully produced using the modified flame spheroidisation setup.
The samarium-doped microspheres, both solid and porous, using phosphate-based glass and poly(lactic acid) matrix, developed in this study are highly promising and have great potential for improving radionuclide microspheres for internal radiotherapy applications. Importantly, the production only involves flame spheroidisation which is rapid, simple, and without hazardous chemicals solvents or radioactive exposure.
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