Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Mar 30, 2020; 10(2): 10-25
Published online Mar 30, 2020. doi: 10.5493/wjem.v10.i2.10
Neutron-activated biodegradable samarium-153 acetylacetonate-poly-L-lactic acid microspheres for intraarterial radioembolization of hepatic tumors
Yin-How Wong, Hun-Yee Tan, Azahari Kasbollah, Basri Johan Jeet Abdullah, Rajendra Udyavara Acharya, Chai-Hong Yeong
Yin-How Wong, Basri Johan Jeet Abdullah, Rajendra Udyavara Acharya, Chai-Hong Yeong, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Hun-Yee Tan, School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Azahari Kasbollah, Medical Technology Division, Malaysian Nuclear Agency, Bangi 43000, Selangor, Malaysia
Rajendra Udyavara Acharya, Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, Singapore 599489, Singapore
Author contributions: Wong YH performed the majority of experiments and analyzed the data; Tan HY assisted the physicochemical and radiolabeling tests; Kasbollah A organized and supervised the neutron activation process; Abdullah BJJ, Acharya RU and Yeong CH designed and coordinated the research; Wong YH and Yeong CH wrote the paper.
Supported by Fundamental Research Grant Scheme sanctioned by the Ministry of Education, Malaysia, No. FRGS/1/2019/SKK06/TAYLOR/02/3.
Institutional review board statement: Not applicable
Institutional animal care and use committee statement: Not applicable.
Conflict-of-interest statement: The authors declared no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Rajendra Udyavara Acharya, PhD, Professor, DEng, Department of Electronics and Computer Engineering, Ngee Ann Polytechnic, 535 Clementi Road, Singapore 599489, Singapore. aru@np.edu.sg
Received: October 20, 2019
Peer-review started: October 20, 2019
First decision: December 17, 2019
Revised: February 14, 2020
Accepted: March 1, 2020
Article in press: March 1, 2020
Published online: March 30, 2020
Abstract
BACKGROUND

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

AIM

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

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Radioembolization, Samarium-153, Yittrium-90, Biodegradable microsphere, Liver tumors, Neutron activation

Core tip: We developed and tested a neutron-activated, biodegradable samarium-153 acetylacetonate-poly-L-lactic acid microspheres formulation for radioembolization of hepatic tumors. The formulation is potentially useful for intraarterial hepatic radioembolization as an alternative to yttrium-90 microspheres due to their biodegradability, favorable physicochemical characteristics and excellent radionuclide retention efficiency. The synthesis of the formulation does not involve ionizing radiation and hence reducing the complication and cost of production.