Evaluation of Therapeutic Efficacy and Imaging Capabilities of SmO-Loaded Polystyrene Microspheres for Intra-Tumoural Radionuclide Therapy of Liver Cancer Using Sprague-Dawley Rat Model.

Neutron-activated samarium-153-oxide-loaded polystyrene ([Sm]SmO-PS) microspheres has been developed in previous study as a potential theranostic agent for hepatic radioembolization. In this study, the therapeutic efficacy and diagnostic imaging capabilities of the formulation was assessed using liver cancer Sprague-Dawley (SD) rat model. Twelve male SD rats (150-200 g) that implanted with N1-S1 hepatoma cell line orthotopically were divided into two groups (study versus control) to monitor the tumour growth along 60 days of treatment. The study group received an intra-tumoural injection of approximately 37 MBq of [Sm]SmO-PS microspheres, while control group received an intra-tumoural injection of 0.1 mL of saline solution. A clinical single photon emission computed tomography/computed tomography (SPECT/CT) system was used to scan the rats at Day 5 post-injection to investigate the diagnostic imaging capabilities of the microspheres. All rats were monitored for change in tumour volume using a portable ultrasound system throughout the study period. Histopathological examination (HPE) was performed after the rats were euthanized at Day 60. At Day 60, no tumour was observed on the ultrasound images of all rats in the study group. In contrast, the tumour volumes in the control group were 24-fold larger compared to baseline. Statistically significant difference was observed in tumour volumes between the study and control groups ( < 0.05). The SPECT/CT images clearly displayed the location of [Sm]SmO-PS in the liver tumour of all rats at Day 5 post-injection. Additionally, the [Sm]SmO-PS microspheres was visible on the CT images and this has added to the benefits of Sm as a CT contrast agent. The HPE results showed that the [Sm]SmO-PS microspheres remained concentrated at the injection site with no tumour cells observed in the study group. Neutron-activated [Sm]SmO-PS microspheres demonstrated excellent therapeutic and diagnostic imaging capabilities for theranostic treatment of liver cancer in a SD rat model. Further studies with different animal and tumour models are planned to validate this finding.