A degradable metal radioactive iodine-125 particle and preparation method thereof

Abstract

The invention discloses a degradable metal radioactive iodine-125 particle and a preparation method thereof, comprising the steps of: placing a degradable metal rod in a hydrofluoric acid aqueous solution in proportion, separating the liquid, soaking it with water, separating the water, and uniformly mixing the obtained metal rod with 0.5-10mCi radioactive iodine-125 sodium aqueous solution, potassium ferrocyanide aqueous solution, soluble magnesium salt aqueous solution and potassium ferrocyanide aqueous solution; reacting at pH=7-10 and room temperature, taking it out, washing it with acetone, and drying it to obtain a degradable metal rod adsorbed with iodine-125; loading the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, welding and sealing at both ends to obtain a degradable metal radioactive iodine-125 particle, and the particle of the invention is degradable; the reaction time is short, the reaction is easy to control, the volatilization of radioactive iodine-125 is small, the utilization rate is high, the dosage is uniform, firm and dense. The production cost is low and the scale is easy.

Description

Technical Field

[0001] The invention belongs to the field of application of radioactive particle implantation therapy for tumor intraradiotherapy, and specifically relates to a degradable metal radioactive iodine-125 particle and a preparation method thereof. Background Art

[0002] Internal radiotherapy radioactive iodine-125 particle implantation treatment technology is to implant radioactive iodine-125 particles into human tumors and surrounding tissues, and use the low-energy X-rays and gamma rays emitted by the radioactive iodine-125 particle source core to continuously kill or injure tumor cells, thereby achieving the purpose of treating tumors. Since radioactive iodine-125 mainly emits X-rays and gamma rays with an energy of 27 to 35Kev, a half-life of 59.4d and a tissue range of 1.7cm, internal radiotherapy radioactive iodine-125 particle implantation treatment technology can effectively kill tumor cells, while the normal tissues around the tumor are less damaged, minimally invasive, and recover quickly, significantly improving the quality of life of patients. It has become the latest international ideal means of treating malignant solid tumors, suitable for early, mid-term and late-stage tumors, and widely used in implantation treatment of tumors such as liver cancer, lung cancer, esophageal cancer and pancreatic cancer.

[0003] At present, the radioactive iodine-125 particles used in internal radiotherapy are very small (length 4.50mm and outer diameter 0.80mm). One implantation treatment requires 30 to 50 radioactive iodine-125 particles to be implanted. Therefore, due to the small size of the particles and the large number of implants, it is not easy to remove them from the body after implantation treatment. In order to avoid patients undergoing surgery again, the implanted radioactive iodine-125 particles are usually retained in the patient's body. The existing radioactive particle products are made by placing iodine-125 adsorbed silver rods or palladium rods into titanium tubes and welding the two ends. Since titanium tubes do not degrade in the body, the radioactive iodine-125 particles will remain intact and permanently in the patient's body after implantation, which will have the following disadvantages: (1) Due to the long half-life of radioactive iodine-125, the residual activity of radioactive iodine-125 particles after treatment will bring additional radiation doses to the normal tissues around the patient's tumor; (2) Although the radioactive iodine-125 particles will be solidified in the calcified lesion tissue after treatment, a very small number of radioactive iodine-125 particles will fall off and migrate to other tissues or organs, posing health risks; (3) After treatment, the radioactive iodine-125 particles will remain in the body, causing various psychological and other pains to the patient and adding a lot of foreign metal substances to the patient. In order to overcome these shortcomings, Chinese patent CN101417135 discloses a method for preparing biodegradable radioactive particles for cancer treatment, wherein a substrate of radioactive particles of the desired shape is prepared using a biocompatible polymer degradable material, a functional group is grafted on the surface of the substrate after modification, an iodine-containing compound is coupled, and a radioisotope-containing substrate is prepared by radioisotope replacement, and finally a modified film is applied to the surface of the radioisotope-containing substrate. Although this method overcomes the shortcomings of existing radioactive iodine-125 particles, it still has the following shortcomings: (1) the preparation process is complicated, with many steps, and it is not easy to control and scale; (2) the reaction time is long (13 to 24 hours), and the utilization rate of iodine-125 is low; (3) the surface of radioactive iodine-125 particles is easily contaminated, and the polymer substrate and the modified film are easily denatured by radioisotope radiation; (4) during the implantation of radioactive iodine-125 particles, the push rod is easy to cause the modified film to be damaged, resulting in radioactive contamination of the operating room, etc. Summary of the invention

[0004] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a degradable metal radioactive iodine-125 particle with simple preparation process, rapid reaction, easy control and safe use.

[0005] The second object of the present invention is to provide a method for preparing degradable metal radioactive iodine-125 particles.

[0006] The technical solution of the present invention is summarized as follows:

[0007] A preparation method of degradable metal radioactive iodine-125 particles, comprising the following steps: placing a degradable metal rod in a 0.2-1 mL, 0.1-0.5 mol / L hydrofluoric acid aqueous solution in proportion and soaking it for 5-10 minutes, separating the liquid, soaking it in water, separating the water, and mixing the obtained metal rod with a 0.5-10 mCi radioactive iodine-125 sodium aqueous solution, 0.01 mL-0.2 mL 0.01-0.1 mg / mL potassium ferrocyanide aqueous solution, and 0.1-0. 5 mL of a 0.01-0.1 mg / mL soluble magnesium salt aqueous solution and 0.01 mL-0.2 mL of a 0.1-1 mg / mL potassium ferrocyanide aqueous solution are uniformly mixed; reacted for 10-120 minutes at room temperature at pH 7-10, taken out, washed with acetone, and air-dried to obtain a degradable metal rod adsorbed with iodine-125; the degradable metal rod adsorbed with iodine-125 is loaded into a degradable metal round tube, and both ends are welded to obtain a degradable metal radioactive iodine-125 particle.

[0008] Preferably, the length of the degradable metal rod is 1 mm to 8 mm, and the diameter is 0.1 mm to 1.5 mm.

[0009] Preferably, the length of the degradable metal round tube is 2.5 mm to 9.5 mm, and the outer diameter is 0.4 mm to 1.8 mm.

[0010] Preferably, the material of the degradable metal rod is magnesium-silver alloy, magnesium-copper alloy, zinc-silver alloy or zinc-copper alloy.

[0011] Preferably, the Ag content of the magnesium-silver alloy is 0.1wt% to 5wt%; the Cu content of the magnesium-copper alloy is 0.1wt% to 5wt%; the Ag content of the zinc-silver alloy is 0.1wt% to 5wt%; the Cu content of the zinc-copper alloy is 0.1wt% to 5wt%.

[0012] Preferably, the soluble magnesium salt is magnesium bromide, magnesium chloride or magnesium iodide.

[0013] Preferably, the material of the degradable metal round tube is magnesium strontium alloy, magnesium zinc alloy, magnesium tin alloy, magnesium silicon alloy, magnesium zinc manganese alloy, magnesium zirconium alloy, magnesium silver alloy, magnesium copper alloy, magnesium zinc rare earth alloy, zinc aluminum copper alloy or zinc iron alloy.

[0014] Preferably, the strontium content of the magnesium-strontium alloy is 0.5wt% to 1.8wt%; the zinc content of the magnesium-zinc alloy is 0.8wt% to 6wt%; the tin content of the magnesium-tin alloy is 0.1wt% to 1.5wt%; the silicon content of the magnesium-silicon alloy is 0.1wt% to 0.8wt%; the zinc content of the magnesium-zinc-manganese alloy is 1wt% to 2.5wt%, and the manganese content is 0.05wt% to 0.8wt%; the zirconium content of the magnesium-zirconium alloy is 0.2wt% to 1.5wt%; t%~5wt%; the silver content of the magnesium-silver alloy is 0.1wt%~5wt%; the copper content of the magnesium-copper alloy is 0.1wt%~1wt%; the zinc content of the magnesium-zinc rare earth alloy is 2wt%~10wt%, and the rare earth content is 0.1wt%~3wt%; the aluminum content of the zinc-aluminum-copper alloy is 1wt%~6wt%, and the copper content is 0.5wt%~5wt%; the iron content of the zinc-iron alloy is 0.05wt%~0.3wt%.

[0015] The method is used to prepare a degradable metal radioactive iodine-125 particle.

[0016] Advantages of the present invention:

[0017] (1) The radioactive iodine-125 particles of the present invention are degradable;

[0018] (2) The method of the present invention uses hydrofluoric acid to age the degradable metal rod, forming an oxide layer as a protective layer on the surface of the degradable metal rod to prevent potassium ferrocyanide from oxidizing the degradable metal rod substrate during the iodination reaction.

[0019] (3) The method of the present invention has a short reaction time, is easy to control, has low volatilization of radioactive iodine-125, and has a high utilization rate of radioactive iodine-125. The prepared radioactive iodine-125 degradable metal rod has a uniform dosage, is firm, and is dense.

[0020] (4) Low production cost and easy scalability;

[0021] (5) After implantation, the metal shell and metal rod of the radioactive iodine-125 particles will degrade in the body, and the radioactive iodine-125 will be excreted from the body in the form of iodine ions, reducing the radiation dose of the residual activity of the radioactive particles to normal tissues;

[0022] (6) The degradation products of degradable metal materials will be absorbed or metabolized by the human body. Therefore, no foreign metal remains in the body after implantation treatment, and the side effects are minimal.

[0023] (7) All the chemical reagents required are readily available. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1The iodine-125 leakage rate of the degradable metal radioactive iodine-125 particles prepared in Example 1 changes with the number of days of storage. DETAILED DESCRIPTION

[0025] The present invention will be further described below by means of specific examples.

[0026] Example 1

[0027] A preparation method of degradable metal radioactive iodine-125 particles comprises the following steps: placing a degradable metal rod in a 0.5 mL, 0.2 mol / L hydrofluoric acid aqueous solution and soaking it for 8 minutes according to a certain proportion, separating the liquid, soaking it in water, separating the water, and uniformly mixing the obtained metal rod with a 5 mCi radioactive iodine-125 sodium aqueous solution, 0.05 mL of a 0.02 mg / mL potassium ferrocyanide aqueous solution, 0.2 mL of a 0.05 mg / mL magnesium bromide aqueous solution, and 0.05 mL of a 0.2 mg / mL potassium ferrocyanide aqueous solution; reacting it at pH=8 and room temperature for 20 minutes, taking it out, washing it with acetone, and drying it to obtain a degradable metal rod adsorbed with iodine-125; and placing the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, and sealing the two ends with welding (argon arc welding, electron beam welding, and laser welding can be adopted, and laser welding is preferred) to obtain a degradable metal radioactive iodine-125 particle.

[0028] The degradable metal rod has a length of 3 mm and a diameter of 0.5 mm and is made of a magnesium-silver alloy having an Ag content of 5 wt %.

[0029] The degradable metal round tube has a length of 4.5 mm and an outer diameter of 0.8 mm. It is made of a magnesium-silver alloy, and the silver content of the magnesium-silver alloy is 2 wt %.

[0030] The radioactivity in the reaction solution was measured with a radioactivity meter and the utilization rate of radioactive iodine-125 was calculated according to the following formula.

[0031] Utilization rate of radioactive iodine-125 = [1-activity of iodine [125I] in reaction solution ÷ activity of iodine [125I] input] × 100%

[0032] The measured radioactivity in the reaction solution was 0.025 mCi, and the utilization rate of radioactive iodine-125 was 99.75%;

[0033] The activity of the degradable metallic radioactive iodine-125 particles is 3.5 mCi.

[0034] In vitro degradation effect of a degradable metal radioactive iodine-125 particle:

[0035] One degradable metal radioactive iodine-125 particle (activity of 3.5 mCi) prepared in Example 1 was placed in 1 mL of 0.9% NaCl aqueous solution and placed at 37°C for 300 days. Starting from the 60th day, 0.1 mL of the solution was taken out every 20 days, and the radioactivity count was measured with a radioimmuno-γ counter. The leakage rate of the radioactive iodine-125 particle was calculated. The test results are shown in FIG. Figure 1 .from Figure 1 In the experiment, the leakage rate of radioactive iodine-125 particles increased with the increase of placement time in 0.9% NaCl aqueous solution, which also shows that the degradable radioactive iodine-125 particles are constantly degrading. When the radioactive iodine-125 particles were placed in 0.9% NaCl solution for 120 days, iodine-125 leakage appeared in the solution, which shows that the degradable metal tube has been degraded. As the placement time increases, the degradable metal tube degrades over a large area, which is manifested in the increase of iodine-125 leakage rate; when the radioactive iodine-125 particles were placed for 180 days, the iodine-125 leakage increased significantly, which shows that the degradable metal tube is basically completely degraded and the degradable metal rod begins to degrade; by 300 days, the iodine-125 leakage rate basically reaches 100%, and the particles are completely degraded.

[0036]

[0037] Example 2

[0038] A preparation method of degradable metal radioactive iodine-125 particles comprises the following steps: placing a degradable metal rod in a 0.2mL, 0.5mol / L hydrofluoric acid aqueous solution and soaking it for 5 minutes according to a proportion, separating the liquid, soaking it in water, separating the water, and evenly mixing the obtained metal rod with a 0.5mCi radioactive iodine-125 sodium aqueous solution, 0.01mL 0.1mg / mL potassium ferrocyanide aqueous solution, 0.1mL 0.1mg / mL magnesium chloride aqueous solution and 0.01mL 1mg / mL potassium ferrocyanide aqueous solution; reacting for 10 minutes at pH=7 and room temperature, taking it out, washing it with acetone, and drying it to obtain a degradable metal rod adsorbed with iodine-125; and placing the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, and welding and sealing the two ends to obtain a degradable metal radioactive iodine-125 particle.

[0039] The degradable metal rod has a length of 1 mm and a diameter of 0.1 mm, and is made of a magnesium-copper alloy, wherein the Cu content of the magnesium-copper alloy is 0.1 wt%;

[0040] The degradable metal round tube has a length of 2.5 mm and an outer diameter of 0.4 mm, and is made of a magnesium-copper alloy, wherein the copper content of the magnesium-copper alloy is 1 wt%;

[0041] The measured radioactivity in the reaction solution was 0.007 mCi, and the utilization rate of radioactive iodine-125 was 98.6%;

[0042] The activity of the degradable metallic radioactive iodine-125 particles is 0.30 mCi.

[0043] Example 3

[0044] A preparation method of degradable metal radioactive iodine-125 particles is characterized by comprising the following steps: placing a degradable metal rod in 1 mL of 0.1 mol / L hydrofluoric acid aqueous solution and soaking it for 10 minutes according to proportion, separating the liquid, soaking it in water, separating the water, and evenly mixing the obtained metal rod with 10 mCi of radioactive iodine-125 sodium aqueous solution, 0.2 mL of 0.01 mg / mL potassium ferrocyanide aqueous solution, 0.5 mL of 0.01 mg / mL magnesium iodide aqueous solution and 0.2 mL of 0.1 mg / mL potassium ferrocyanide aqueous solution; reacting for 120 minutes at pH=10 and room temperature, taking it out, washing it with acetone, and drying it to obtain a degradable metal rod adsorbed with iodine-125; and placing the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, and welding and sealing the two ends to obtain a degradable metal radioactive iodine-125 particle.

[0045] The degradable metal rod has a length of 8 mm and a diameter of 1.5 mm and is made of a zinc-silver alloy having an Ag content of 5 wt %.

[0046] The degradable metal round tube has a length of 9.5 mm and an outer diameter of 1.8 mm. It is made of zinc-iron alloy, and the iron content of the zinc-iron alloy is 0.3 wt%.

[0047] The measured radioactivity in the reaction solution was 0.165 mCi, and the utilization rate of radioactive iodine-125 was 98.35%;

[0048] The activity of the degradable metallic radioactive iodine-125 particles is 5.5 mCi.

[0049] Example 4

[0050] A preparation method of degradable metal radioactive iodine-125 particles comprises the following steps: placing a degradable metal rod in a 0.5 mL, 0.2 mol / L hydrofluoric acid aqueous solution and soaking it for 8 minutes according to a certain proportion, separating the liquid, soaking it in water, separating the water, and evenly mixing the obtained metal rod with a 5 mCi radioactive iodine-125 sodium aqueous solution, 0.05 mL of a 0.02 mg / mL potassium ferrocyanide aqueous solution, 0.2 mL of a 0.05 mg / mL magnesium bromide aqueous solution, and 0.05 mL of a 0.2 mg / mL potassium ferrocyanide aqueous solution; reacting it for 20 minutes at pH=8 and room temperature, taking it out, washing it with acetone, and drying it to obtain a degradable metal rod adsorbed with iodine-125; and placing the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, and welding and sealing the two ends to obtain a degradable metal radioactive iodine-125 particle.

[0051] The degradable metal rod has a length of 1 mm and a diameter of 0.20 mm and is made of a zinc-copper alloy, wherein the Cu content of the zinc-copper alloy is 0.1 wt %.

[0052] The degradable metal round tube has a length of 2.5 mm and an outer diameter of 0.45 mm. It is made of a magnesium-zinc alloy, and the zinc content of the magnesium-zinc alloy is 6 wt %.

[0053] The measured radioactivity in the reaction solution was 0.038 mCi, and the utilization rate of radioactive iodine-125 was 99.24%;

[0054] The activity of the degradable metallic radioactive iodine-125 particles is 3.2 mCi.

[0055] Experiments show that the material of the degradable metal rod is selected from: magnesium-silver alloy with an Ag content of 0.1wt%, magnesium-silver alloy with an Ag content of 2wt%, magnesium-copper alloy with a Cu content of 2wt%, magnesium-copper alloy with a Cu content of 5wt%, zinc-silver alloy with an Ag content of 0.1wt%, zinc-silver alloy with an Ag content of 2wt%, zinc-copper alloy with a Cu content of 2wt%, and zinc-copper alloy with a Cu content of 5wt%, which replace the zinc-copper alloy with a Cu content of 0.1wt% in this embodiment, and the rest is the same as in this embodiment, and degradable metal radioactive iodine-125 particles are prepared respectively, and the activity is 3.2±0.2mCi; the utilization rate of radioactive iodine-125 is more than 98%.

[0056] Experiments have shown that the material of the degradable metal round tube is selected from a magnesium-strontium alloy with a strontium content of 1wt%; a magnesium-strontium alloy with a strontium content of 0.5wt%; a magnesium-strontium alloy with a strontium content of 1.8wt%; a magnesium-zinc alloy with a zinc content of 0.8wt%; a magnesium-zinc alloy with a zinc content of 3wt%; a magnesium-tin alloy with a tin content of 1wt%; a magnesium-tin alloy with a tin content of 0.1wt%; a magnesium-tin alloy with a tin content of 1.5wt%; a magnesium-silicon alloy with a silicon content of 0.5wt%; a magnesium-silicon alloy with a silicon content of 0.1wt%; a magnesium-silicon alloy with a silicon content of 0.8wt%; a magnesium-zinc-manganese alloy with a zinc content of 2wt%; a magnesium-zinc-manganese alloy with a manganese content of 0.2wt%; a magnesium-zinc-manganese alloy with a zinc content of 1wt%; a magnesium-zinc-manganese alloy with a manganese content of 0.05wt%; a magnesium-zinc-manganese alloy with a zinc content of 2.5wt%; a magnesium-zinc-manganese alloy with a manganese content of 0.8wt%; and a zirconium content of 1wt%. 3wt% magnesium-zirconium alloy; magnesium-zirconium alloy with zirconium content of 0.2wt%; magnesium-zirconium alloy with zirconium content of 5wt%; magnesium-silver alloy with silver content of 0.1wt%; magnesium-silver alloy with silver content of 5wt%; magnesium-copper alloy with copper content of 0.1wt%; magnesium-copper alloy with copper content of 0.5wt%; magnesium-zinc rare earth alloy with zinc content of 5wt% and rare earth content of 1wt%; magnesium-zinc rare earth alloy with zinc content of 2wt% and rare earth content of 0.1wt%; magnesium-zinc rare earth alloy with zinc content of 10wt% and rare earth content of 3wt%; aluminum-copper alloy with aluminum content of 3wt% and copper content of 3wt%; aluminum-copper alloy with aluminum content of 1wt% and copper content of 0.5wt%; aluminum-copper alloy with aluminum content of 6wt% and copper content of 5wt%; zinc-iron alloy with iron content of 0.05wt%. Zinc-iron alloy with iron content of 0.1wt%. By replacing the zinc content of the present embodiment with 6wt% magnesium-zinc alloy, and keeping the other aspects the same as the present embodiment, a corresponding degradable metal radioactive iodine-125 particle was prepared, with an activity of 3.2±0.2mCi and a radioactive iodine-125 utilization rate of more than 98%.

Claims

1. A method for preparing degradable metal radioactive iodine-125 particles, characterized in that The method comprises the following steps: placing a degradable metal rod in a 0.2-1 mL, 0.1-0.5 mol / L hydrofluoric acid aqueous solution in proportion and soaking it for 5-10 minutes, separating the liquid, soaking it in water, separating the water, and mixing the obtained metal rod with a 0.5-10 mCi radioactive iodine-125 sodium aqueous solution, 0.01 mL-0.2 mL 0.01-0.1 mg / mL potassium ferrocyanide aqueous solution, and 0.1-0.5 mL 0.01- 0.1 mg / mL soluble magnesium salt aqueous solution and 0.01 mL to 0.2 mL potassium ferrocyanide aqueous solution with a concentration of 0.1 to 1 mg / mL are uniformly mixed; reacting for 10 to 120 minutes at pH = 7 to 10 and room temperature, taking out, washing with acetone, and drying to obtain a degradable metal rod adsorbed with iodine-125; placing the degradable metal rod adsorbed with iodine-125 into a degradable metal round tube, and welding and sealing both ends to obtain a degradable metal radioactive iodine-125 particle; The material of the degradable metal rod is magnesium-silver alloy, magnesium-copper alloy, zinc-silver alloy or zinc-copper alloy; The material of the degradable metal round tube is magnesium strontium alloy, magnesium zinc alloy, magnesium tin alloy, magnesium silicon alloy, magnesium zinc manganese alloy, magnesium zirconium alloy, magnesium silver alloy, magnesium copper alloy, magnesium zinc rare earth alloy, zinc aluminum copper alloy or zinc iron alloy.

2. The preparation method according to claim 1, characterized in that The length of the degradable metal rod is 1 mm to 8 mm, and the diameter is 0.1 mm to 1.5 mm.

3. The preparation method according to claim 1, characterized in that The degradable metal round tube has a length of 2.5 mm to 9.5 mm and an outer diameter of 0.4 mm to 1.8 mm.

4. The preparation method according to claim 1, characterized in that The Ag content of the magnesium-silver alloy is 0.1wt% to 5wt%; the Cu content of the magnesium-copper alloy is 0.1wt% to 5wt%; the Ag content of the zinc-silver alloy is 0.1wt% to 5wt%; the Cu content of the zinc-copper alloy is 0.1wt% to 5wt%.

5. The preparation method according to claim 1, characterized in that The soluble magnesium salt is magnesium bromide, magnesium chloride or magnesium iodide.

6. The preparation method according to claim 1, characterized in that The strontium content of the magnesium-strontium alloy is 0.5wt% to 1.8wt%; the zinc content of the magnesium-zinc alloy is 0.8wt% to 6wt%; the tin content of the magnesium-tin alloy is 0.1wt% to 1.5wt%; the silicon content of the magnesium-silicon alloy is 0.1wt% to 0.8wt%; the zinc content of the magnesium-zinc-manganese alloy is 1wt% to 2.5wt%, and the manganese content is 0.05wt% to 0.8wt%; the zirconium content of the magnesium-zirconium alloy is 0.2wt% to 1.5wt%; %~5wt%; the silver content of the magnesium-silver alloy is 0.1wt%~5wt%; the copper content of the magnesium-copper alloy is 0.1wt%~1wt%; the zinc content of the magnesium-zinc rare earth alloy is 2wt%~10wt%, and the rare earth content is 0.1wt%~3wt%; the aluminum content of the zinc-aluminum-copper alloy is 1wt%~6wt%, and the copper content is 0.5wt%~5wt%; the iron content of the zinc-iron alloy is 0.05wt%~0.3wt%.

7. A degradable metal radioactive iodine-125 particle prepared by the method of any one of claims 1 to 6.

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