Synthesis of Holmium-166-alginate microspheres using extrusion dripping and emulsification methods

Abstract

Ho-166-alginate microspheres could present a new type of device for the radioembolisation of liver cancer, where targeted radiation therapy is combined with embolisation of tumour blood vessels. Whereas current devices in radioembolisation are permanent, alginate offers a biodegradable device with a cheap and simple production process. The isotope holmium-166 has been of interest in radiotherapy due to its favourable half-life and decay through β-emission. Furthermore, its paramagnetic properties allows visualisation using Magnetic Resonance Imaging (MRI) and its γ-emission allows for imaging using Single Photon Emission Computed Tomography (SPECT). This research investigates the synthesis, loading efficiency and stability of Ho-166-alginate microspheres. For synthesis of alginate microspheres, this research uses the extrusion dripping method and emulsification method. Here, process parameters are investigated to crosslink alginate with Ca²⁺ and to obtain alginate particles having diameter of around 30 μm. In the extrusion dripping method, increasing pH showed crosslinking of alginate into viscous gel formations or alginate particles having a wrinkled surface. A pH of 4 offered the best conditions to produce spherical alginate particles with smoother surface morphology and smallest particle size. Particle size below 100 μm was not obtained in the extrusion dripping method, but the emulsification method in this research succeeded in particle formation with sizes between 10 to 60 μm. The Ca-alginate microspheres from the emulsification method were further used in an ion-exchange process to replace the Ca²⁺ in the alginate structure with Ho³⁺. Using Ho-166, an average loading efficiency of (86.5 ± 1.4)% was found. The obtained Ho-166-alginate microspheres were tested on their radiochemical stability in demiwater and 0.9% NaCl solution. Here, the microspheres in demiwater showed excellent stability, whereas their retention percentage in 0.9% NaCl decreased to ~60% after five minutes. Nevertheless, the retention percentage in 0.9% NaCl further remained stable for up to 24 hours. Further research could include stabilizing the alginate microspheres post-emulsification, as removal of surfactant during washing steps resulted in an increase of particle size. Secondly, investigation on process parameters within the emulsification method could bring the particle size between 20 to 60 μm with a smaller size distribution. Destined for radioembolisation, the Ho-166-alginate microspheres need improved loading efficiency and improved stability in physiological media such as 0.9% NaCl. Literature on Ho-alginate microspheres is very limited as of now, and this research takes a step towards Ho-166-alginate microspheres as radioembolic device for transarterial radioembolisation.