Abstract
Glioblastoma is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. Internal radiotherapy, also called brachytherapy, is an advanced cancer treatment where radioactive seeds are placed in or near the tumor itself, giving a high radiation dose to the tumor while reducing the radiation exposure in the surrounding healthy tissues. Among the available radioactive materials, 166Ho emits high-energy β radiation required for tumor destruction and low-energy γ radiation which can be used for quantitative SPECT imaging. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. In this context, we synthesized 400 nm particles via a sol-gel process in acidic conditions using holmium (III) oxide Ho2O3 as a nanostructured precursor. The objective was to design particles with a high 165Ho content combined with an enhanced stability suitable for brachytherapy of brain cancer following neutron activation. A sol-gel process was chosen to make Ho2O3 soluble in aqueous media and to improve particle’s colloidal stability. The resulting suspension showed enhanced colloidal stability in water, as evidenced by zeta potential and sedimentation rate measurements, combined with a high Ho content (28% w:w). Injectability and preliminary acute toxicity of the suspension were assessed after stereotactic injection in the brain of healthy minipig. Computerized tomography (CT) imaging was performed to visualize the injection sites and to determine the holmium distribution. It turns out that our suspension provided high 165Ho concentration to the site of action by way of stereotactic injection. This procedure allowed identifying suitable experimental conditions for future intratumoral injections of activated suspension.
Highlights
Most common types of tumor treatments include surgery, chemotherapy and/or external radiotherapy
Radioactive seeds may be produced under the shape of microspheres doped with β- emitting radionuclides; this technique is known as micro-brachytherapy [2]
Particle size was determined by Dynamic Light Scattering; suspension was diluted in a polyol solvent of moderate viscosity, i.e. diethylene glycol (DEG, 37.5 mPa.s at 25°C), to limit sedimentation following dilution
Summary
Most common types of tumor treatments include surgery, chemotherapy and/or external radiotherapy. Internal radiotherapy ( called brachytherapy) is an advanced cancer treatment. Radioactive seeds may be produced under the shape of microspheres doped with β- emitting radionuclides; this technique is known as micro-brachytherapy [2]. Its incidence is 2-3 per 100,000 adults per year in the US and Europe and approximately 13,000 cases are diagnosed each year in Europe. It shows the worst prognosis of all brain cancers because surgical resection of entire tumors is almost impossible [3]. The market for radiation therapy equipment is expected to reach US$8 billion by 2020 due to rising incidence of cancer and increasing preference for non-surgical treatment options [5]
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