¹³¹I-labeled chitosan hydrogels for radioembolization: A preclinical study in small animals

The purpose of the study was to examine potential of ¹³¹I-labeled chitosan hydrogels (Chi) for treatment of liver cancer.

Orthotopic hepatoma was induced by McA-RH7777-fLuc cells (1×10⁷) that were injected into the left hepatic lobe of rats. Ten days later, tumor-bearing rats evidenced by bioluminescence received ¹²⁵I-labeled Chi with left hepatic artery access. Pharmacokinetics and excretion (n=8) and biodistribution (n=6/time point) were studied after injection. To examine therapeutic potential, animals (n=8/group) were also treated with Chi labeled with or without ¹³¹I. Changes in tumor volume by magnetic resonance (MR) imaging were studied.

The rate of tumor induction assessed by bioluminescence imaging was 72% (68/95). Gamma counter and scintigraphy imaging analyses showed accumulation of ¹²⁵I-labeled Chi dominantly in the liver. A small fraction of ¹²⁵I-labeled Chi was detected in the stomach (2.02±3.07%ID) and muscle (1.37±1.48%ID) at 2 d post-treatment. Blood sample analysis showed the maximum blood concentration of 0.09±0.03%ID/mL, which peaked at 0.60±0.45 d. Over a 4-week period, 31.22±8.16%ID were excreted in the urine and 3.5±1.3% in the feces. Treatment of Chi (median, 876mm³; IQR, 496mm³-1413mm³) markedly reduced the extent of tumor growth, compared to controls (median, 12,085mm³; IQR, 7786mm³-25,832mm³; P<0.05 vs control). ¹³¹I Chi (median, 80mm³; IQR, 35mm³-172mm³; P<0.05 vs control) induced a greater tumor-suppressing effect, compared to Chi alone.

In this study, we have characterized a new radioembolization device, ¹³¹I Chi, in vivo and provided evidence for its therapeutic potential.

Transarterial embolization is a conceivable treatment option for patients with inoperable liver cancer to mitigate the disease progression. Recently, we have developed chitosan-based hydrogel microparticles. In the present study, the hydrogel microparticles were radiolabeled with ¹³¹I for treatment of liver cancer. Our results demonstrated that a hepatic arterial injection of ¹²⁵I-labeled Chi resulted in substantial liver accumulation, which was accompanied by virtually no extrahepatic deposition. The results of the present study also showed that administration of ¹³¹I Chi markedly suppressed tumor growth, compared to controls and to animals receiving unlabeled Chi. ¹³¹I-labeled chitosan hydrogel microparticles represent a new therapeutic approach for treatment of liver cancer.