Liver cancer is the 6^th most common cancer in the world and the 4^th most common death from cancer worldwide. Hepatic radioembolization is a minimally invasive treatment involving intraarterial administration of radioembolic microspheres.

To develop a neutron-activated, biodegradable and theranostics samarium-153 acetylacetonate (¹⁵³SmAcAc)-poly-L-lactic acid (PLLA) microsphere for intraarterial radioembolization of hepatic tumors.

Microspheres with different concentrations of ¹⁵²SmAcAc (i.e., 100%, 150%, 175% and 200% w/w) were prepared by solvent evaporation method. The microspheres were then activated using a nuclear reactor in a neutron flux of 2 × 10¹² n/cm²/s¹, converting ¹⁵²Sm to Samarium-153 (¹⁵³Sm) via ¹⁵²Sm (n, γ) ¹⁵³Sm reaction. The SmAcAc-PLLA microspheres before and after neutron activation were characterized using scanning electron microscope, energy dispersive X-ray spectroscopy, particle size analysis, Fourier transform infrared spectroscopy, thermo-gravimetric analysis and gamma spectroscopy. The in-vitro radiolabeling efficiency was also tested in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.

The SmAcAc-PLLA microspheres with different SmAcAc contents remained spherical before and after neutron activation. The mean diameter of the microspheres was about 35 µm. Specific activity achieved for ¹⁵³SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc after 3 h neutron activation were 1.7 ± 0.05, 2.5 ± 0.05, 2.7 ± 0.07, and 2.8 ± 0.09 GBq/g, respectively. The activity of per microspheres were determined as 48.36 ± 1.33, 74.10 ± 1.65, 97.87 ± 2.48, and 109.83 ± 3.71 Bq for ¹⁵³SmAcAc-PLLA microspheres with 100%, 150%, 175% and 200% (w/w) SmAcAc. The energy dispersive X-ray and gamma spectrometry showed that no elemental and radioactive impurities present in the microspheres after neutron activation. Retention efficiency of ¹⁵³Sm in the SmAcAc-PLLA microspheres was excellent (approximately 99%) in both 0.9% sodium chloride solution and human blood plasma over a duration of 550 h.

The ¹⁵³SmAcAc-PLLA microsphere is potentially useful for hepatic radioembolization due to their biodegradability, favorable physicochemical characteristics and excellent radiolabeling efficiency. The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.

• Radioembolization
• Samarium-153
• Yittrium-90
• Biodegradable microsphere
• Liver tumors
• Neutron activation

• MRI
• colon
• constipation
• dysmotility
• imaging
• irritable bowel syndrome
• small intestinal bacterial overgrowth
• transit

• II-LB-0814-20002 Department of Health

Introduction: Transarterial radioembolization (TARE) has been proven as an effective treatment for unresectable liver tumor. In this study, neutron activated, ¹⁵³Sm-labeled microspheres were developed as an alternative to ⁹⁰Y-labeled microspheres for hepatic radioembolization. ¹⁵³Sm has a theranostic advantage as it emits both therapeutic beta and diagnostic gamma radiations simultaneously, in comparison to the pure beta emitter, ⁹⁰Y. Methods: Negatively charged acrylic microspheres were labeled with ¹⁵²Sm ions through electrostatic interactions. In another formulation, the Sm-labeled microsphere was treated with sodium carbonate solution to form the insoluble ¹⁵²Sm carbonate (¹⁵²SmC) salt within the porous structures of the microspheres. Both formulations were neutron-activated in a research reactor. Physicochemical characterization, gamma spectrometry, and radiolabel stability tests were carried out to study the performance and stability of the microspheres. Results: The Sm- and SmC-labeled microspheres remained spherical and smooth, with a mean size of 35 µm before and after neutron activation. Fourier transform infrared (FTIR) spectroscopy indicated that the functional groups of the microspheres remained unaffected after neutron activation. The ¹⁵³Sm- and ¹⁵³SmC-labeled microspheres achieved activity of 2.53 ± 0.08 and 2.40 ± 0.13 GBq·g⁻¹, respectively, immediate after 6 h neutron activation in the neutron flux of 2.0 × 10¹² n·cm⁻²·s⁻¹. Energy-dispersive X-ray (EDX) and gamma spectrometry showed that no elemental and radioactive impurities were present in the microspheres after neutron activation. The retention efficiency of ¹⁵³Sm in the ¹⁵³SmC-labeled microspheres was excellent (~99% in distilled water and saline; ~97% in human blood plasma), which was higher than the ¹⁵³Sm-labeled microspheres (~95% and ~85%, respectively). Conclusion: ¹⁵³SmC-labeled microspheres have demonstrated excellent properties for potential application as theranostic agents for hepatic radioembolization.

• Samarium-153
• liver tumour
• microspheres
• neutron activation
• radioembolization
• radiopharmaceutical