RU2443030C2 - TECHNETIUM-99m GENERATOR WITH SULFO-CARBOXYLATED CATION-EXCHANGING PROTECTIVE LAYER AND THE METHOD OF ITS PRODUCTION - Google Patents

Abstract

FIELD: nuclear medicine.

SUBSTANCE: technetium-99m generator for production of sterile radiopharmaceutical Technetium-99m contains chromatography column with sorbent packaged in layers one of the layers of which contains aluminum oxide in acidic form, another layer contains silica gel modified by manganese oxide (IV), on the output the chromatographic channel contains cation-exchanging protective layer. On the output chromatographic layer contains cation-exchanging protective layer made of sulfo-carboxylated super high molecular polyethylene with dispersity from 0.14 to 0.25 mm in Na-form. Method of production of Technetium-99m generator. Technetium-99 radiopharmaceutical has been eluted by the passage of the sodium chloride isotonic solution through the column with the carrier containing adsorbed molybdenum-99 radionuclide, packaged in the elution direction with the layer containing silicagel modified with dioxide of manganese (IV) and the layer containing aluminum oxide. Techentium-99m is eluted through the column with the carrier that is additionally packaged on the outlet with the later containing sulfo-carboxylated super high molecular polyethylene in Na-form that is produced by graft copolymerization of acrylic acid and styrenesulfonic acid to super high molecular polyethylene.

EFFECT: increased speed of eluate filling from generator with maintained or higher degree of eluate purity from Mn²⁺ cations.

3 cl, 3 ex, 1 tbl

Description

Field of the invention: the invention relates to a method for manufacturing radioisotope generators, in particular, to an industrial method for producing a technetium-99m ( ^99m TC) generator used in nuclear medicine for diagnostic purposes.

Analysis of the current level of knowledge in this area shows that the ^99m Tc chromatographic column generators in which the parent radionuclide molybdenum-99 ( ⁹⁹ Mo), isolated from the fission products of uranium in the form of molybdate ions, are adsorbed on the surface of the sorbent, and the resulting during its radioactive decay, the daughter radionuclide ^99m Te in the form of pertechnetate ions is eluted with physiological saline (0.9% NaCl solution).

The closest analogue in technical essence to the claimed method for producing a ^99m Tc generator is a method for producing a technetium-99m generator, in which the technetium-99t radionuclide is eluted with physiological saline through a column with a carrier containing a molybdenum-99 adsorbed radionuclide, packed in the direction of elution with a layer containing silica gel modified with manganese (IV) dioxide and a layer containing alumina in acidic form and an additionally packed layer containing carboxyl anny polyethylene in Na-form. In this case, carboxylated polyethylene is obtained by graft polymerization of acrylic acid to low pressure polyethylene. Technetium-99m generator for producing a sterile technetium-99m radio product containing a chromatographic column with a sorbent packed in layers, one of the layers of which is made of aluminum oxide in acid form, the other layer contains silica gel modified with manganese (IV) oxide, and the chromatographic column is at the output contains a cation exchange protective layer of carboxylated polyethylene in Na-form. The chromatographic column contains a cation exchange protective layer of carboxylated polyethylene in the Na form with a dispersion of 0.05-0.1 mm (Ru 2342722). Obtaining carboxylated polyethylene with a given dispersion is provided by a known method of passing a polyethylene powder through a sieve.

The efficiency of using a technetium-99 t generator depends on the rate of filling of the eluate from the generator while maintaining the required degree of purity of the eluate from Mn ²⁺ cations. A higher filling rate of the eluate from the generator allows medical personnel to spend less time directly next to the ionizing radiation source. The cation exchange protective layer of the chromatographic column with greater dispersion reduces the resistance to the flow of the eluate and allows you to increase the speed of filling the eluate from the generator. However, an increase in the degree of dispersion while maintaining the overall dimensions of the chromatographic column will lead to a decrease in the mass of the cation exchange protective layer. This, in turn, can lead to a decrease in the capture efficiency of Mn ²⁺ cations, i.e. to a decrease in the purity of the eluate. In addition, a smaller fraction of the protective layer can lead to contamination with particles of the eluate.

The objective of the proposed solution is to increase the efficiency of using a technetium-99m generator. The technical result is an increase in the rate of filling of the eluate from the generator while maintaining or a higher degree of purity of the eluate from Mn ²⁺ cations.

The problem is solved by the method of producing a technetium-99m generator, in which the technetium-99m radionuclide is eluted with physiological saline through a column with a carrier containing an adsorbed molybdenum-99 radionuclide, packed in the direction of elution with a layer containing silica gel modified with manganese dioxide and a layer containing alumina in acidic form, technetium-99m radionuclide is eluted through a column with a support additionally packed at the outlet with a layer containing a sulfo-carboxylated ultra-high molecular weight unitary polyethylene in Na-form, which is obtained by graft copolymerization of acrylic acid and sodium styrene sulfonate to ultra-high molecular weight polyethylene.

A copolymer of acrylic and styrenesulfonic acid prevents the release of Mn ²⁺ cations into the eluate more efficiently than polyacrylic acid.

It is proposed to replace low-pressure polyethylene with ultra-high molecular weight polyethylene, which has a higher density and improved mechanical properties. Firstly, particles of ultra-high molecular weight polyethylene during the preparation of the cation exchange sorbent will not be destroyed, and, therefore, a fine fraction will not form, which in the future may lead to contamination of the eluate. Secondly, the use of ultra-high molecular weight polyethylene in graft polymerization will lead to the preferential localization of grafted ionogenic groups on the surface of the particles, and not in the entire particle volume, as in the case of using low density polyethylene. Thus, the localization of grafted ionogenic groups on the surface of particles of ultra-high molecular weight polyethylene will increase the number of ion-exchange groups per unit mass of the cation-exchange protective layer, which also increases the elution efficiency per unit mass of the cation-exchange protective layer.

Thus, an increase in the number of ion-exchange groups per unit mass of the cation-exchange protective layer due to the use of ultra-high molecular weight polyethylene and the introduction of additional stronger sulfo groups to the carboxyl groups makes it possible to reduce the cation-exchange protective layer and increase the rate of filling of the eluate from the generator.

The problem is also solved by the technetium-99m generator to obtain a sterile radiopharmaceutical of technetium-99m, which contains a chromatographic column with a sorbent packed in layers, one of the layers of which contains aluminum oxide in acid form, the other layer contains silica gel modified with manganese (IV) oxide, At the output, the chromatographic column contains a cation exchange protective layer of sulfo-carboxylated ultra-high molecular weight polyethylene, with a dispersion of 0.14 to 0.25 mm, in the Na form. The technetium-99m generator is produced by a method in which a sulfo-carboxylated ultra-high molecular weight polyethylene with a fineness of 0.14 to 0.25 mm is obtained by passing an ultra-high molecular weight polyethylene powder through a sieve in ethanol under the influence of ultrasonic waves and grafting copolymerization of acrylic acid and sodium styrene sulfonate to ultra high molecular weight polyethylene.

Under the influence of ultrasonic waves in ethanol, the powder of ultra-high molecular weight polyethylene with a fraction of 0.14 to 0.25 mm does not stick together and freely passes through a sieve in the form of a suspension.

Moreover, an increase in the dispersion of ultra-high molecular weight polyethylene to 0.14-0.25 mm will not lead to a deterioration in the quality of the eluate for Mn ^{2+ ions} .

Figure 1 presents a schematic diagram of a device for producing a sterile technetium-99m generator. Figure 1 shows: 1 - column for packaging; 2 - case; 3 - layer containing silica gel, modified with manganese oxide (IV); 4 - layer of aluminum oxide in acidic form; 5 - cation exchange protective layer of sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form; 6 - distance ring; 7 - filter material; 8 - distribution layer; 9 - permeable plug; 10 - sealing metal cap.

Example 1

Obtaining ultra-high molecular weight polyethylene with a fraction of 0.14-0.25 mm

Ultra-high molecular weight polyethylene in the amount of 3.6-4.2 g of dry powder was transferred to a sieve with a mesh size of 40 μm, the titanium rod of the ultrasonic disintegrator was lowered into the sieve so that the lower end of the rod was 5-8 mm from the sieve mesh. Ethyl alcohol was poured into a sieve to such a level that the titanium rod was immersed in alcohol by 3-4 cm, sounded by ultrasound (ultrasonic power 100 W) for 40-50 minutes. At the same time, a constant level of ethyl alcohol was maintained in the sieve by continuously pumping it with a peristaltic pump. Particles less than 0.25 mm in size were collected in a receiving flask in the form of a suspension in ethyl alcohol. Then, a suspension of particles in ethanol was passed through a sieve with a mesh size of 0.14 mm and the operation was repeated in the same manner as on a sieve with a mesh size of 0.25 mm. The sieving process was carried out until no particles with sizes less than 0.14 mm remained on the sieve. At the same time, 0.14-0.25 mm particles remained on the 0.14 mm sieve. Particles of 0.14-0.25 mm in size were dried in a vacuum oven (60 mm Hg) at a temperature of 95 ° C for 1 hour. The above particle sieving operation was carried out repeatedly until the desired fraction was obtained in an amount of 20 g. All obtained fractions were combined and additionally similarly sieved particles through a sieve with mesh sizes of 0.14 mm. The consumption of alcohol for sieving particles amounted to 5200 cm ³ . The sieved particles of 0.14-0.25 mm were dried in a vacuum oven at 95 ° C for 2 hours.

The yield of particles 0.14-0.25 mm in size was 10-15% of the initial high molecular weight polyethylene powder. The number of particles in the range of 0.14-0.25 mm was at least 95%.

Example 2

Obtaining sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form.

A 0.14-0.25 mm ultra-high molecular weight polyethylene powder fraction was irradiated on a ⁶⁰ Co gamma-ray apparatus in an air atmosphere to an absorbed dose of 150 kGy at a dose rate of 0.1-1.0 Gy / s. Acrylic acid was grafted onto irradiated ultrahigh molecular weight polyethylene from its aqueous solution in the presence of ferrous salts. Synthesis conditions: acrylic acid concentration - 75 vol.%; concentration of Fe ²⁺ - 1 g / dm; temperature - 85 ° C; the duration of polymerization is 90 minutes Then, ultra-high molecular weight polyethylene grafted polyethylene was kept in a 1 M aqueous solution of sodium styrene sulfonate for 24 h at room temperature. Then, ⁶⁰ Co was irradiated on a gamma installation to an absorbed dose of 0.6 kGy at a dose rate of 0.1-0.2 Gy / s at atmospheric pressure and room temperature. The obtained sulfo-carboxylated ultra-high molecular weight polyethylene was converted into the Na form, passing through a layer of cation exchanger 1 N. NaOH solution in the ratio: per 1 volume of ion exchanger 20 volumes of alkali. The static exchange capacity of the synthesized sulfo-carboxylated ultra-high molecular weight polyethylene, determined by NaOH, was 5.0 ± 0.1 mmol per 1 g of air-dry cation exchange resin.

Example 3

Obtaining sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form.

A 0.14-0.25 mm ultra-high molecular weight polyethylene powder fraction was irradiated on a ⁶⁰ Co gamma-ray apparatus in an air atmosphere to an absorbed dose of 150 kGy at a dose rate of 0.1-1.0 Gy / s. Acrylic acid was grafted onto irradiated ultrahigh molecular weight polyethylene from its aqueous solution in the presence of ferrous salts. Synthesis conditions: concentration of acrylic acid - 75 vol.%; the concentration of Fe ²⁺ is 1 g / dm ³ ; temperature - 85 ° C; the duration of polymerization is 120 minutes Next, ultra-high molecular weight grafted polyacrylic acid polyethylene was kept in a 1 M aqueous solution of sodium styrene sulfonate for 24 hours at room temperature. Then, ⁶⁰ Co was irradiated on a gamma installation to an absorbed dose of 0.6 kGy at a dose rate of 0.1-0.2 Gy / s at atmospheric pressure and room temperature. The obtained sulfo-carboxylated ultra-high molecular weight polyethylene was converted into the Na form, passing through a layer of cation exchanger 1 N. NaOH solution in the ratio: per 1 volume of ion exchanger 20 volumes of alkali. The static exchange capacity of the synthesized sulfo-carboxylated ultra-high molecular weight polyethylene, determined by NaOH, was 5.8 ± 0.1 mmol per 1 g of air-dry cation exchange resin.

Example 4

Obtaining a technetium-99m generator

The chromatographic column of the generator is packed in three layers (in the direction of elution: silica gel, modified MnO ₂ - 0.55 g, dispersion - 0.14-0.25 mm; alumina - 0.67 g, dispersion - 0.063-0.2 mm; the sulfo-carboxylated ultra-high molecular weight polyethylene obtained in example 2 is 0.33 g, the dispersion is 0.14-0.25 mm, the static exchange capacity for NaOH is 5.0 ± 0.1 mmol per 1 g of air-dry cation exchange resin. The pH of the solution to adsorb ⁹⁹ Mo - 2-3 Activity adsorbed ⁹⁹ Mo production day -. 49 ± 2,6 GBq (nominal - 28.5 ± 1.5 GBq, two days predkalib . Ovki) Elution was performed two days later eluate Radiochemical purity - 99,8 ± 0,1%; pH of the eluate - 6.3 ± 0.2.

Example 5

Obtaining a technetium-99m generator

The chromatographic column of the generator is packed in three layers according to example 3, where the sulfo-carboxylated ultra-high molecular weight polyethylene obtained in example 3 is 0.33 g, the dispersion is 0.14-0.25 mm, the static exchange capacity by NaOH is 5.8 ± 0 , 1 mmol per 1 g of air-dry cation exchanger.

The generalized results on the composition and dispersion of the cation-protective layer, the rate of filling of the eluate from the generator, the analysis of the eluate on the removal of manganese cations Mn ²⁺ in comparison with the prototype are shown in the table.

Prototype Example 3 Example 4 The composition of the cation exchange protective layer Carboxylated Polyethylene in Na Form Sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form Sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form The dispersion of the cation exchange protective layer, mm 0.05-0.1 0.14-0.25 0.14-0.25 Static exchange capacity for NaOH, mmol per 1 g of air-dry cation exchange resin 3.2 ± 0.1 5.0 ± 0.1 5.8 ± 0.1 The mass of the cation exchange protective layer, g 0.5 0.33 0.33 The activity of adsorbed eluate, GBK (elution two days after receipt) 24 ± 1,2 24 ± 1,2 24 ± 1,2 Removal of manganese cations Mn ²⁺ 2.5 ± 0.2 1.8 ± 0.2 1.8 ± 0.2 The rate of filling of the eluate from the generator, ml / min 5 2 four

Claims (3)

1. Technetium-99m generator for producing a sterile radiopharmaceutical technetium-99m, containing a chromatographic column with a sorbent packed in layers, one of the layers of which contains aluminum oxide in acid form, the other layer contains silica gel modified with manganese (IV) oxide, the chromatographic column is at the output contains a cation exchange protective layer, characterized in that the output of the chromatographic column contains a cation exchange protective layer of sulfo-carboxylated ultra-high molecular weight polyethylene with Fineness from 0.14 to 0.25 mm, in Na-form. 2. A method of producing a technetium-99m generator, in which the technetium-99m radionuclide is eluted with physiological saline through a column with a carrier containing an adsorbed molybdenum-99 radionuclide, packaged in the direction of elution with a layer containing silica gel modified with manganese (IV) dioxide and a layer containing oxide aluminum in acid form, technetium-99m radionuclide is eluted through a column with a carrier additionally packed at the outlet with a cation exchange protective layer, characterized in that technetium-99m radionuclide is eluted through a column with a carrier packed at the outlet by a cation exchange protective layer containing sulfo-carboxylated ultra-high molecular weight polyethylene in Na-form, which is obtained by graft copolymerization of acrylic acid and sodium styrene sulfonate to ultra-high molecular weight polyethylene. 3. The method according to claim 2, characterized in that the sulfo-carboxylated ultra-high molecular weight polyethylene with a dispersion of from 0.14 to 0.25 mm is obtained by passing the powder of ultra-high molecular weight polyethylene through a sieve in ethyl alcohol under the influence of ultrasonic waves and grafting copolymerization of acrylic acid and styrene sulfonate sodium to ultra high molecular weight polyethylene.