Therapeutic Effect of I-131-labeled Chitosan Hydrogels on Treatment of Hepatic Cancer: Focused on In vivo Rodent Orthotopic Hepatic Cancer Models

Objectives Hepatocellular carcinoma (HCC) results in substantial morbidity and mortality. It is known that surgical resection offers the best chance for cure in HCC. For patients with surgically unresectable HCC, radioembolization often shows therapeutic promise. The purpose of the study was to assess the effect of I-131-labeled chitosan hydrogels (I-131-Chi) on the treatment of HCC.

Methods HCC was induced by injection of the McA-RH7777-fLuc (1 × 10⁷) cell line into the left liver lobe of rats. Fifteen days later, the animals received Chi labeled with I-125 (I-125-Chi) via hepatic artery injection. The biodistribution was assessed using a gamma counter and scintigrafic imaging at various time points (1, 2, 4, 7, 14, and 28 days after treatment). To examine therapeutic effectiveness, Chi with and without I-131 was administered via hepatic artery injection. Changes in tumor volume and glucose metabolism were studied. The differences in mean values before and 4 weeks after treatment were compared.

Results I-125-Chi was mainly present in the liver without leakage to other organs throughout the course of the study. The liver radioactivity measured by gamma counting and confirmed by scintigraphy was 36±8% injected dose (ID) at day 1, 40±7%ID at day 2, 31±3%ID at day 4, 19±6%ID at day 7, 17±3%ID at day 14, and 13±1%ID at day 28 after treatment. Over the 4 week periods, I-125-Chi was eliminated mainly though urine (31±8%ID) and feces (3.5±1.3%ID). In control group (no treatment), the mean tumor volume measured by MRI was increased 21-fold from baseline. Treatment of Chi alone markedly reduced the extent of tumor growth and increased the volume only to a 1.1-fold from baseline. I-131-Chi showed a greater tumor inhibitory effect as evidenced by a 4-fold reduction from baseline. Post-mortem examination also confirmed the MRI findings (R²=0.933). ¹⁸F-FDG PET image analysis revealed that there was a 1.2-fold increase in SUV_max values in both control and Chi groups. I-131-Chi decreased the SUV_max value to 1.6-fold from baseline.

Conclusions Our data demonstrate effective tumor inhibitory effects of I-131-Chi and the therapeutic promise in treating HCC.