Novel Silicone-Coated 125I Seeds for the Treatment of Extrahepatic Cholangiocarcinoma

Abstract

125I seeds coated with titanium are considered a safe and effective interstitial brachytherapy for tumors, while the cost of 125I seeds is a major problem for the patients implanting lots of seeds. The aim of this paper was to develop a novel silicone coating for 125I seeds with a lower cost. In order to show the radionuclide utilization ratio, the silicone was coated onto the seeds using the electro-spinning method and the radioactivity was evaluated, then the anti-tumor efficacy of silicone 125I seeds was compared with titanium 125I seeds. The seeds were divided into four groups: A (control), B (pure silicone), C (silicone 125I), D (titanium 125I) at 2 Gy or 4 Gy. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human extrahepatic cholangiocarcinoma cell line FRH-0201 and tumor-bearing BALB/c nude mice. The silicone 125I seeds showed higher radioactivity; the rate of cell apoptosis in vitro and the histopathology in vivo demonstrated that the silicone 125I seeds shared similar anti-tumor efficacy with the titanium 125I seeds for the treatment of extrahepatic cholangiocarcinoma, while they have a much lower cost.

Fig 1. Diagrams illustrating the experimental design: (a) coaxial electrospinning device, silver-silicone with ¹²⁵I in syringe1, another silicone in syringe2 as the shell, the jets forming the core—shell structure; (b) the principle diagram of seeds, the outside layer is the silicone coating the ¹²⁵I solution inside(c,d) the anti-tumor effect of the silicone was examined in vitro and in vivo using human cell line FRH-0201 and tumor-bearing BALB/c nude mice.

Fig 2. Silicone ¹²⁵I seeds, the diameter and length was 0.8 mm by 4.5 mm.

Fig 3

A.The irradiation model was placed in the incubator. B. Eight ¹²⁵I seeds were fixed on the dish around the 35 mm diameter circumference, with one ¹²⁵I seed placed at the center of dish. C. A 35mm culture dish was placed on the top of the irradiation model.

Fig 4. Operative procedure for the seed implantation into the tumor: (a) the mouse was given a implantation of seed by tweezers; (b) the seed was implanted into the tumor.

Fig 5. The radioactivity comparison of s-¹²⁵I seeds and t-¹²⁵I seeds.

The radioactivity of s-¹²⁵I is higher than t-¹²⁵I obviously.

Fig 6. Evaluation of the in vitro anti-tumour effects of ¹²⁵I seeds.

(a) and (b)apoptotic progression in FRH-0201 cell lines in response to the titanium ¹²⁵I seeds and silicone ¹²⁵I seeds treatment for 2Gy and 4Gy; (c) cell FACS distributions (%) of apoptotic cells in different groups. Quadrant Q1,Q2,Q3 and Q4 reflect necrosis, late apoptosis, alive and early apoptosis, respectively.Total apoptosis includes late apoptosis plus early apoptosis. There was not significance between titanium ¹²⁵I seeds and silicone ¹²⁵I seeds groups. * P <0.05 means 4Gy compared with the 2 Gy groups respectively.

Fig 7. Investigation into the in vivo anti-tumor effects of the ¹²⁵I seeds: (a,b)graphs of tumor growth and mice weight change after treatment with titanium ¹²⁵I seeds and silicone ¹²⁵I seeds in vivo.

Fig 8. Anti-tumor effects of the ¹²⁵I seeds by TUNEL staining:(a)the red spots represented the apoptotic cells detected by TUNEL staining in the each groups. The average number of apoptotic cells per 100 objective fields were plotted.(b) *P < 0.05 compared with the control group.

#P < 0.05 compared with the pure silicone group.

Fig 9. HE staining.

The tumor histopathology for all ¹²⁵I seeds and pure silicone groups after treatment. Tissue necrosis and ischemia were most frequently observed in the control and pure silicone groups, the silicone and titanium ¹²⁵I groups showed very few necrotic or apoptotic cells were observed in the tumors.