99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Yi Dong; Lingling Yin; Jintao Huang; Di Hu; Jing Sun; Zhe Zhang; Zhihao Li; Bin-Yan Zhong; Ran Zhu; Guanglin Wang

doi:10.1016/j.mtbio.2024.101367

^99mTc/⁹⁰Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Mater Today Bio. 2024 Nov 27:29:101367. doi: 10.1016/j.mtbio.2024.101367. eCollection 2024 Dec.

Authors

Yi Dong¹, Lingling Yin¹, Jintao Huang², Di Hu², Jing Sun¹, Zhe Zhang¹, Zhihao Li¹, Bin-Yan Zhong², Ran Zhu¹, Guanglin Wang¹

Affiliations

¹ State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
² Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Abstract

Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of ^99mTc and therapeutic radionuclide of ⁹⁰Y. Both ^99mTc radiolabeled HAMS (^99mTc-HAMS) and radiolabeled ⁹⁰Y-HAMS (⁹⁰Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability in vitro and in vivo. ^99mTc-HAMS are highly effective in assessing the LSF, while ⁹⁰Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both ^99mTc-HAMS and ⁹⁰Y-HAMS have promising clinical applications in HCC theranostics.

Keywords: Biodegradable microspheres; Hepatocellular carcinoma; Lung shunt fraction assessment; Radioactive microspheres; Transarterial radioembolization.