Abstract
1248
Objectives: Radionuclide-labeled microspheres, such as Y-90 and P-32 labeled glass microspheres have already been used for radioembolization for hepatocellular carcinoma (HCC); however, limited treatment effect after complete decay of radionuclides and incapable multiple embolizations are still great challenge because of the non-biodegradable component of microspheres. Thus, radionuclide-labeled microspheres with proper biodegradable period matches radionuclide decay time could be a better choice. This study developed a novel iodine-131-labeled microsphere with ideal biodegradable time, and its radioembolization effect in orthotopic primary hepatocellular carcinoma rat was evaluated.
Methods: The composited microspheres were prepared with collagen and chitosan. The characteristics of collagen-chitosan microspheres (CCMs) were determined by scanning electron microscope (SEM). The stability of 131I-CCMs was evaluated in saline and human blood serum for up to 30 days, and its biodegradation in those solutions were measured. 131I-radiolabelled microspheres were interventionally injected into hepatocellular livers through hepatic artery in rats. The in vivo stability of 131I-CCMs was assessed by histological analysis and SPECT. The anti-tumor effects of microspheres were assessed by liver MRI, post operation survival(POS) and histological analysis from tissue specimen.
Results: Composited microspheres were successfully obtained with desirable shapes and particle size of 10-20 μm by SEM measurement (Fig.1). Every 1mg of microspheres was able to carry about 50mCi of iodine-131 and radiolabeling efficiency of 92.82% was achieved by TLC analysis. SPECT indicated consistent stability of CCMs in liver through 28 days until iodine-131 was biologically metabolized while other organs are barely rose (Fig.2 A, B). Furthermore, the radioembolization by 131I-microspheres significantly prolonged POS from 19±7 d to 28±15d(Fig.3), and less focuses were observed by MRI and histological analysis (Fig.4 A, B, C; Fig.5 A, B, C).
Conclusions: The biodegradable 131I-labeled CCMs were successfully prepared and exhibited high radiolabeling efficiency and ideal stability in vitro and in vivo. Favorable prolonged survival time against primary HCC in rats was observed by radioembolization of 131I-CCMs, suggesting this might be a potential drug for interventional radionuclide cancer therap. Key words: 131I; Hepatocellular Carcinoma; Microsphere; Collagen; Chitosan; Radioembolization.Research Support: This project was partly supported by Sichuan Provincial Department of Science and Technology Support Program (20135Y0009 to Li, L and 2016HH0065 to Cai H) and National Science Fund of China (81301250 to Cai, H).Fig. 1. CCMs were detected by SEM before injection. Microspheres with smooth and desirable shape (diameter 10~20μm) were prepared by emulsification-chemical crosslinking method (1000X). Fig. 2. SPECT imaging performed on 7d, 14d, 21d and 28d in 131I-CCMs group after administration of 131I-CCMs (A) while on 1d, 2d, 3d, 4d, (B) after the administration of 131I-NaI in 131I-NaI group. Fig. 3. Kaplan-Meier curve showing the POS in control group, sham-operation group and 131I-CMMs group.Fig. 4. MRI imaging performed in 0W, 1W, 2W, 3W, 4W in control group(A) and after administration of 131I-CCMs and saline respectively in sham-operation group(B) and 131I-CCMs group(C).Fig. 5. Liver tissue specimen were collected on day 1W,2W,3W and 4W in control group(A) and after administration of saline and 131I-CCMs respectively in sham-operation group(B) and 131I-CCMs group(C).
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.