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

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.