Mass Production of Source Core for Iodine-125 Seed

Experimental Section

Surface Modification of Ag Rod. For mass production, 100 Ag rods were used as a batch in all experiments. The cut rods were etched by 3 M HNO3 at 70 °C until the surface changes white color. Then, all rods were immersed in 15 mL of the solution contained 0.610 M sodium phosphate (Na3PO4) and 0.084 M hydrogen peroxide (H2O2) as an oxidant for 24 hours at room temperature to modify the surface with PO4 3−. For comparison, another set of rods was treated with chloride (Cl−), as reported in the literature.8

Iodine-Adsorption on Ag Rod. Each set of 100 rods was immersed in 5 mL of 0.01 M sodium hydroxide (NaOH) solution containing non-radioactive iodide (127I) and 131I (half-life 8.02 days) as the tracer instead of 125I in a 5 mL vial. The radioactivity of the non-radioactive iodide and tracer was equivalent to 14800 MBq (400 mCi, calculated by previous report15) and 14800 kBq (400 μCi) of 125I, respectively. The vials were rotated with a roll mixer at a speed of 200 rpm for 24 h at room temperature. The solution was then removed, and the rods were washed with a saline solution and deionized water. The activities of the rods were measured individually by the HPGe detector (ORTEC Inc. GEM 20P4-70).

Leachability Test. For the leachability test, 5 rods adsorbed with 131I were selected randomly and placed individually in 1 mL of deionized water or serum albumin for 48 h at room temperature. Then, the activities of the 0.5 mL of the solution were measured by using the HPGe detector.

 

Results and Discussion

For an effective iodide-adsorption on Ag rods, a novel method was developed using a phosphate intermediate.15 To prepare phosphorylated Ag rods, Ag rods were reacted with a sodium phosphate solution under a strong oxidant not containing chlorine, e.g., H2O2. When H2O2 is added to the solution, at first, the silver surface is oxidized to form an ionized atmosphere, Ag rod-Ag+, and the phosphate ions then react with its surface at the same time. To increase the surface area, a surface etching was performed using 3 M HNO3 for about 2 min before the phosphorylation. Iodination was carried out by simply mixing the phosphorylated Ag rods and iodide solution. In previous reports for chlorinated intermediate, the exchange reaction can be explained by using Ksp value.5,8 In general, a lower Ksp, e.g., AgI, 8.52 × 10−17, shows robust precipitation to the silver surface after forming an exchange reaction with a higher Ksp substance, e.g., AgCl, 1.77 × 10−10. However, the substitution reaction of phosphate with iodine cannot be explained by Ksp. This mechanism, we hypothesized, is based on the distortion effect that phosphate, PO4 3−, would bind to the surface without its own angles. The angle strain easily induces the substitution reaction with iodine ions. To find the optimum condition of iodide adsorption on a Ag surface, 10 Ag rods were used in our previous study. The profiles of the rods treated with various anions (N3 −, CO3 2−, C2O4 2−, AsO4 3−, Cl− and PO4 3−) are as shown in Figure 3. Only the PO4 3−-based rods retained glossy silver color, whereas those of N3 −, CO3 2−, C2O4 2− and Cl− had dark grey colors and AsO4 3− was dark brown without luster. It was observed that PO4 3−-based Ag rods adsorbed 137.90 MBq (3.7269 mCi), which was the highest efficiency, > 74%, and 4.5 times greater than that of Cl--based Ag rods at a 0.5 mL volume of 100 mCi/mL solution. 15

Figure 3.Profiles of the Ag rods treated with various anions.

In this study on the mass production of the source cores, all subsequent tests were carried out using the phosphorylation method, and 100 rods were used in each test. First, the iodide-adsorption efficiency was confirmed in comparison with the chlorinated rods as a reference8 under the same experimental condition, and the result is presented in Table 1. The PO4 3−-based rods could take up to ~ 70% (102.60 MBq (2.773 mCi)) of the iodine activity from the contact solution, which was 1.9 times higher than the activity of Cl−-based rods, 54.21 MBq (1.465 mCi). There is a difference between the two cases of using 10 rods and 100 rods. This may be because the friction among many rods rotating fast in the vial occurs frequently, and also found that the reproducibility of the chlorination method is very low.

Table 1.amaximum adsorbable activity of iodide is 148 MBq/rod (4 mCi/rod) in all tests. baverage adsorbed activity of rod. cE = average adsorbed activity/maximum adsorbable activity

As a quality assurance of the sources, a leachability test before encapsulation for checking leached iodine from rods, and a leak test after encapsulation for checking the sealing condition, should be carried out. In this report, a leachability test was performed by randomly choosing 5 rods of (a) and (b) in Table 1. When H2O was used, the obtained results show that the iodine from the surface of the rods leached 0.06%, and 0.23%, respectively. From these results, it could be found that PO4 3−-based Ag rods firmly adsorb iodide and show a safer and more stable state in the aqueous solution. On the other hand, an additional test was carried out with serum albumin, plasma protein in humans, and the results revealed that more than 30% of the activities of both rods were leached in the test solutions. Therefore, in the case of radioisotope-leakage of therapeutic seeds, a leak test is a very essential part along with the leachability test. It should be performed after sealing the rods and before implanting the seeds into the human body.

Figure 4 shows the adsorption activity distribution charts of the rods cut by using a cutting device and by handmade. When using the cutting device, the number of rods having an average of ± 5% activities was 55, which is higher than that of handmade cutting. The reason may be that the rods having a fixed length of 3 mm (l) can be uniformly fabricated by the cutting device. In addition, this enables producing the uniform rods more easily and quickly. These advantages can render the distribution of activities relatively focused in same batches, and the total production time of 125I seed can be shortened during mass production.

Figure 4.Distribution charts for the adsorbed activities of the rods ((a) production by hand, (b) by cutting device).

The effect of iodide concentration in the solutions was investigated with 100 rods manufactured by the cutting device, and the results are depicted in Figure 5. Various iodine solutions in 5 mL volume of 0.01 M NaOH were used. It was found that the iodide adsorption ratio was increased according to the iodine concentration. The highest loaded activity was 199.73 MBq/rod (5.398 mCi/rod), and the efficiency was > 77% in the 140 mCi/mL (700 mCi/5 mL) solution, but not reached the saturation point. It is possible that the source cores of higher activity are produced at a higher concentration. The numbers of rods having an average of ± 5% activities were 51, 47, 57, 47, 55, 58 and 45, beginning at the left in Figure 5, and the proportion obtained was approximately 50% of all 100 rods. To obtain a dense distribution of the rod activity and the higher obtainment, various reaction tools has been being studied.

Figure 5.The average adsorbed activity and the number of the rods having average ± 5% activities at various concentrations of iodide (All rods were cut by cutting device).

Conclusion

In conclusion, the mass production of the source core inside the 125I seed was performed using phosphate-based Ag rods. The 125I source core fabricated by using this method is more advantageous than other methods in terms of quantitative iodide-adsorption yield, iodine-leachability, and stability of iodine activity in H2O due to the formation of robust adsorption between Ag rods and iodide. Furthermore, the specially designed cutting device is very useful for mass production of rods owing to its easy, fast, and high reproducibility. The combination of these two techniques based on the phosphate modification of Ag rod and the special cutting device can effectively abbreviate the radioactive wastes and total time consumption during mass production of source core. This report suggests a novel direction for the preparation of 125I seeds used for prostate or eye cancer treatments. Recently, a sealing technology by laser welding and a leak test of seeds are under investigation at our institute.