TW201312593A - Composition method of gallium-68 radioactive nuclide generator - Google Patents

Abstract

The present invention provides a novel composition method of gallium-68 radioactive nuclide generator, which uses two kinds of dissociation washing liquids to respectively obtain novel germaniums of gallium-68 radioactive nuclide with different chemical forms by washing with two kinds of germanium-68 adsorbents, respectively, comprising a first means for extracting hydrochloric acid solution from a dissociation washing liquid bottle and passing the same through an inorganic resin adsorbent tube pillar to generate the radioactive isotope solute gallium-68, and a second means for passing the radioactive isotope solute gallium-68 gallium citrate solution through an organic resin adsorbent tube pillar and allowing the same to flow through a silica gel extraction absorbing tube, which is then washed by the hydrochloric acid solution in the dissociation washing liquid bottle, so as to obtain the radioactive isotope solute gallium-68 gallium tri-chloride solution.

Description

Fabrication method of gallium-68 radioactive nuclear generator

The invention relates to a novel composition method of a gallium-68 radioactive nuclear generator, that is, two kinds of washing liquids respectively pass through two kinds of strontium-68 adsorbents, and the novel hydrazines of different chemical forms of gallium-68 nucleus can be eluted separately.

Due to the long half-life of the mother nucleus 68-68, the 锗-68/gallium-68 nucleus generator can be used for more than one year, and the gallium-68 nucleus can be stably supplied.

In the past, 锗-68 was adsorbed to an inorganic substance such as cerium oxide, aluminum oxide or tin dioxide to prepare a gallium-68 nuclear generator. These are inconvenient to use, for example, if the generator is made of alumina as a sorbent tube, it is necessary to elute the nucleus gallium-68 with EDTA (ethylediaminetetraacetic acid) solution. Since gallium-68-EDTA is a fairly stable structurally complex, some complicated procedures are required to convert gallium-68 into nuclear medicine. Due to the short half-life of gallium-68, the conversion procedure causes dose depletion. If the generator is made of tin oxide as the adsorption tube, the sub-nuclear gallium-68 needs to be eluted with a HCl solution of 1 N or more. At this time, the gallium-68 nucleus is present in the chemical form of gallium chloride, and is used after neutralization. However, trace inorganic salts are dissolved by a strong acid (HCl concentration greater than 1N) solution, which is likely to cause metal ion contamination. The convenience is that it is easy to carry out the labelling work of the gallium-68 nucleus and the Ligand labelling.

The gallium-68 nuclear generator is prepared by adsorbing yttrium-68 with an inorganic substance such as cerium oxide, aluminum oxide or tin dioxide. The common features are as follows: (1) a solution of a high concentration of strong acid (HCl concentration greater than 1 N) Existence (2) easy to cause metal ion pollution (3) If the chemical form of gallium-68-gallium citrate is required, it is time consuming and the radiation dose received by the operator is high, which is not conducive to the production or clinical use of the drug. (4) When the gallium-68 nucleus is present in the chemical form of gallium chloride, it cannot be directly used directly in the clinic. It is necessary to carry out the labelling work of the gallium-68 nucleus and the ligand.

The gallium-68 nuclear generator made by adsorbing yttrium-68 with organic resin has the following characteristics: (1) it is necessary to wash the gallium-68 nucleus with dilute sodium citrate or sodium phosphate solution (2) with gallium-68-citric acid The chemical form of gallium exists (3) It is not easy to cause metal ion pollution. (4) If the chemical form of gallium-68-gallium chloride is required, it is time consuming and the radiation dose received by the operator is high, which is not conducive to the production of the drug. Or clinical use.

The application of Gallium-68 nucleus in PET nuclear medicine is becoming more and more widespread. The single-ion form of gallium-68 nuclear generator is not enough for the application of multi-developed gallium-68 nuclear medicine, and the current literature and patent invention. For example, U.S. Patent Application Serial No. 12/745,715, which is based on the purification of Fe(III) from an automated device, produces a single chemical type of gallium-68 nucleus; in addition, U.S. Patent Application Serial No. 60/928,723 utilizes a rinsing and sorbent column. Multiple purification operations to produce a single chemical type of gallium-68 nucleus, without the operation of combining two different eluents and two different sorbent columns as described in the present invention, obtaining gallium of different chemical forms - 68 nuclear species, namely gallium-68 gallium citrate and gallium-68 gallium chloride.

The object of the present invention is to propose a novel gallium-68 radionuclear generator assembly method, that is, two kinds of eluent respectively can be used to separately elute different chemical forms of gallium-68 nuclear species through two kinds of cesium-68 adsorbents. After the -68 / gallium - 68 nuclear generator.

The application of Gallium-68 nucleus in PET nuclear medicine is becoming more and more widespread. The single-ion form of gallium-68 nuclear generator is not enough for the application of multi-developed gallium-68 nuclear medicine, and the current literature and patent invention, and In the absence of the present invention, the novel 锗-68/gallium-68 nucleus generators of different chemical forms of gallium-68 nucleus were separately eluted by two kinds of eluents through two 锗-68 adsorbents. Gallium-68 gallium citrate solution or gallium-68 gallium chloride solution, which can be used to chelate the radioisotope solution with the chelating agent DotA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) .

The invention utilizes an organic resin to adsorb 锗-68, and when the gallium-68 nucleus is eluted with a dilute sodium citrate or a sodium phosphate solution, the metal ion-contaminated elution liquid is not generated, and the gallium-68 nucleus is in the chemical form of gallium citrate. Existence, although the application range is narrower than gallium-68-gallium chloride, the advantage is that the metal ion content is relatively slight, and the total amount of strontium-68 is about 0.0004%.

In addition, the gallium-68 nucleus is suitable for use in PET (positive angiography) nuclear medicine molecules, for example, by cross-linking with ligands or peptides or a certain protein. Covalent bonding, can be used for angiographic applications of tumor imaging diagnosis.

Gallium-68 is a daughter nucleus produced when 锗-68 decays. The half-life of 锗-68 is 271 days, and the maximum energy is 511KeV. It is produced by gallium-69 by cyclotron radiation, and the nuclear reaction is ⁶⁹ Ga(p, 2n) ⁶⁸ Ge, gallium. -68 half-life of 68.1 minutes, maximum energy β ⁺ = 1.89MeV, gallium-68 due to short half-life, and decay in the form of positrons, mainly used in the preparation of nuclear diagnostics for the diagnosis of nuclear medicine, and is very suitable for the absence of cyclotron Used by hospitals or research units.

The object and the feature of the present invention is that a combination of two different eluents and two different adsorbent columns can obtain different chemical types of gallium-68 nucleus, namely gallium-68 gallium citrate and gallium. -68 gallium chloride. The first figure is a block diagram of the operation flow used in the gallium-68 generator of the present invention, in which two kinds of washing liquids are respectively used to wash out the details of different chemical forms of gallium-68 nuclear species through two kinds of strontium-68 adsorbents. The description is shown in the second figure.

As shown in the second figure, the method of the present invention comprises: (1) a first eluent bottle 1 containing 0.1 M sodium citrate solution sodium citrate (2) a second eluent bottle 2, containing 0.1M hydrochloric chloride (3) styrene-divinylbenzene copolymer column (4) inorganic resin adsorbent column 4 (TiO2 column) (5) silicone extracting adsorption tube 5 (silica -gel cartridge) (6) sodium citrate stock 6 (sodium citrate stock). Two chemical forms of radioisotope solution are generated by the foregoing method, including (7) a radioactive isotope solution gallium-68 gallium citrate solution 7, and (8) a radioactive isotope solution gallium-68 gallium chloride solution 8, which can be used for PET imaging Versatile applications for different application areas such as diagnostics.

The gallium-68 gallium citrate can be obtained in two ways as shown in the second figure: the first one, the sodium citrate solution in the first eluent bottle 1 is taken out and passed through the organic resin adsorbent column. After 3, the radiation isotope solution gallium-68 gallium citrate solution 7 is discharged; the second, the radiation isotope solution gallium-68 gallium chloride solution 8 is passed through the sodium citrate solution 6, and mixed with the sodium citrate solution 6, The radioactive isotope solution gallium-68 gallium citrate solution 7' can be obtained.

The gallium-68 gallium chloride is obtained, as shown in the second figure, in two ways: first, the hydrochloric acid solution in the second rinse bottle 2 is taken out and passed through the inorganic resin adsorbent column 4 , the radiation isotope solution gallium-68 gallium chloride solution 8; the second, the radiation isotope solution gallium-68 citrate solution 7 is passed through the organic resin adsorbent column 3, and then passed through the silicone extraction adsorption tube 5, Then, the radioactive isotope solution gallium-68 gallium chloride solution 8' is obtained by washing away with the hydrochloric acid solution in the second eluent bottle 2.

In the foregoing method, the on-off valve 51 and the on-off valve 52 shown in the second figure are simultaneously opened or closed, and the on-off valve 61 and the on-off valve 62 are simultaneously opened or closed.

1. . . First wash bottle

2. . . Second wash bottle

3. . . Organic resin adsorbent column

4. . . Inorganic resin adsorbent column

5. . . Silicone extraction adsorption tube

51, 52, 61, 62. . . Switch valve

6. . . Sodium citrate solution

7,7'. . . Radioactive isotope solution gallium-68 gallium citrate solution

71, 81. . . Switch valve

8,8'. . . Radioactive isotope solution gallium-68 gallium chloride solution

Figure 1 is a block diagram showing the operational flow used by the gallium-68 generator of the present invention.

Figure 2 is a structural view of the gallium-68 structure of the present invention.

1. . . First wash bottle

2. . . Second wash bottle

3. . . Organic resin adsorbent column

4. . . Inorganic resin adsorbent column

5. . . Silicone extraction adsorption tube

6. . . Sodium citrate solution

7,7'. . . Radioactive isotope solution gallium-68 gallium citrate solution

8,8'. . . Radioactive isotope solution gallium-68 gallium chloride solution

Claims (7)

A method for fabricating a 锗-68/gallium-68 nuclear generator comprising six parts: (1) a first eluent device (2) a second eluent device (3) an organic resin sorbent column ( Styrene-divinylbenzene copolymer column) (4) inorganic resin adsorbent column (TiO2 column) (5) silica-gel cartridge (6) sodium citrate stock (sodium citrate stock), used to make two A chemical form of a radioisotope solution. According to the composition method of the 锗-68/gallium-68 nuclear generator according to the first paragraph of the patent application, wherein the first eluent bottle contains liquid, sodium citrate solution and a concentration of about 0.1 M. The second eluent bottle is filled with a liquid, a hydrochloric acid solution and a concentration of about 0.1 M, wherein the concentration of the eluate depends on the type of eluent used. According to the composition method of the 锗-68/gallium-68 nuclear generator according to the first aspect of the patent application, the first eluent device is configured to extract the sodium citrate solution in the eluent device and pass it through the organic After the resin adsorbent column, the radiation isotope solution gallium-68 gallium citrate solution is discharged. According to the method of constructing the 锗-68/gallium-68 nuclear generator of the third paragraph of the patent application scope, the radiation isotope solution gallium-68 gallium citrate solution is passed through the silicone extraction adsorption tube, and the second wash away The solution of the hydrochloric acid in the liquid device is washed away to obtain a gallium-68 gallium chloride solution of the radioactive isotope solution. According to the composition method of the 锗-68/gallium-68 nuclear generator according to the first aspect of the patent application, the second eluent device is configured to extract the hydrochloric acid solution in the eluent device and adsorb it through the inorganic resin. After the column of the agent, the radiation isotope solution gallium-68 gallium chloride solution is discharged. According to the novel composition method of the 锗-68/gallium-68 nuclear generator according to the fifth paragraph of the patent application scope, the radiation isotope solution gallium-68 gallium chloride solution is passed through a sodium citrate solution and a sodium citrate solution After mixing, a radioactive isotope solution gallium-68 gallium citrate solution can be obtained. According to the composition method of the 锗-68/gallium-68 nuclear generator according to the first application of the patent scope, the radiation isotope solution generated refers to a gallium-68 gallium citrate solution or a gallium-68 gallium chloride solution, which can be used. A radioisotope solution chelated with a chelate compound DotA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid).