방사선의학 웹진

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Abstract

INTRODUCTION:

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

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

ADVANCES IN KNOWLEDGE:

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.

​Author information​​

Hwang H1, Kim KI2, Kwon J1, Kim BS2, Jeong HS1, Jang SJ2, Oh PS1, Park HS3, Lim ST1, Sohn MH1, Jeong HJ4.

1 Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea.

2 Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.

3 Department of Pathology, Chonbuk National University Medical School.

4 Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. Electronic address: jayjeong@jbnu.ac.kr.