CS201754B1 - Production method of injection solution of the bengalese red indicated by radioactive iodine izotope - Google Patents

Description

The present invention provides a method for the production of a solution of Bengal red labeled with an radioactive isotope of iodine used in nuclear medicine for the functional examination and imaging of the liver.

Bengal red is an organic dye containing a mixture of halogenated fluoresceins, predominantly tetrachlorotetraiodofluorescein, tetrachlorotriiodofluorescein, tetraehlorodiodofluorescein, or dichlorodiodofluorescein. The composition of Bengali red brands is not uniform. From the nuclear medicine point of view, where practically quantitative capture of dye from blood to liver is used, the most suitable component of the mixture is tetrachlorotetrajodofluorescein. Therefore, the Czechoslovak Pharmacopoeia 3 requires that a solution of Bengal Red, labeled with a radioactive iodine isotope, contain at least 70 radioactivity in the form of tetrachlorotetrajodofluorescein.

The fact that Bengal red is a blend of a series of halogenated fluoresceins, whose composition varies from manufacturer to manufacturer, raises a number of difficulties in labeling. Bengal red radioactive iodine for nuclear medical use. Labeling of Bengal red with radioactive iodine is a complicated process in which two basic types of reactions are likely to be involved: first, iodination reactions, in which the lower iodinated fluoresceins convert to the higher iodinated by the iodinating agents, which contain some radioactive iodine atoms. The second type of reactions are exchange reactions in which the non-radioactive iodine atom in the iodinated fluorescein molecule is replaced by the radioactive iodine atom.

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The composition of the Bengali red starting substance decisively determines both the quality of the Bengali red labeled with radioactive iodine and the yield of the label.

One of the first reports of Bengal red labeling with radioactive iodine ^ J is the work of Liebstra and Andrysk in Nature 184. 913 (1959). The authors worked at pH 5 in the presence of hydrogen peroxide. Raban and Gregora described in International Journal of Applied Radiation and Isotopes 19: 361-367 (1968) elemental iodine labeling in an ethanol-abrasion medium. In their further work, published in Nuolear Medicine 257-265 (1968), ee mentions the very different composition of Bengal reds and the resulting different behavior in the body. Therefore, some sutori, such as Desai and Hegesippe, purify Bengal red before use, as reported in the International Journal of Applied Radiation and Isotopes 19: 153-155 (1968). High yield of 99 phy »was achieved by Suner and Mitta, who worked in ethanolic solution at pH 4 and published this work in CNEA - 234 (1969). 590-591 (1966). They study in more detail the course of the labeling of Stanko and Irošnikova in an article published in Isotopenpraxis 8, 592-258, (1972). They use iodine chloride labeling. First they tested the composition of Bengal reds of various brands. Some of them were chosen for further experiments, in which they measured the dependence of yield on concentration of individual reactants and pH. Another concurrent work is that of Hallab and Haieh in Isotopenpraxis 2, 4 (1966). They study the influence of a number of reaction conditions - pH, heat, reaction times, reactant concentrations, specific activities - on the course of the reaction.

When evaluating the existing methods, it is found that

- in all cases, a mixture of iodinated chlorofluoresceins is used as the starting material.

This leads to a non-uniform product, which causes inconvenience in the preparation, control and use of the preparation.

- methods of preparation are relatively complex and time-consuming; most of the time, not all of the radioactive iodine is consumed to label Bengali red and must be removed from the reaction mixture - usually by laborious overcoating. The reaction time is usually several hours and therefore the total preparation time is up to several days.

- due to the long preparation time of the labeled Bengal red, nuclide ^ I, which is no longer promising in terms of the patient's radiation load, is still mostly used.

- methods using elemental radioactive iodine are harmful to work safety.

These disadvantages are eliminated by the method for producing the injection solution of Rose Bengal radiolabelled iodine according to the invention in which to prepare it uses pre-prepared non-radioactive reaction mixture consisting of a solution tatrachlorotetrajodo fluorescein at a concentration of 10 ~ ^ to 10 ^- ^ mol / l acetate buffer with a pK 4 to 6 and hydrogen peroxide at a concentration of 10 to 1 mol / l, to which 10 to 500 MBq of radioactive sodium iodide solution is added, and the resulting solution is mixed, if necessary, at a temperature of 50 to 100 ° C in a 1: 5 to 1:20 with a second preformed solution containing non-radioactive sodium dihydrogen phosphate at 10 _ _- □ -is to 10 ~ ° mol / complexone or 3 at a concentration of 10 "to 10 mol / l.

In the method of making the injectable solution according to the invention, unlike the prior art methods, chromatographically pure tetrachlorotetraiodofluorescein is used, resulting in a uniform product. The high radiochemical yield makes it possible to transfer the preparation to a pre-prepared kit where it is not necessary to remove unreacted iodide. Bftagal red labeling by the method of the invention is very simple, saves time and can be performed directly in the workplace by nuclear medioins. Non-radioactive kits may be readily available for several weeks, provided they are stored at 0 to 4 ° C.

The kit prepared by the process according to the invention is particularly suitable for isotope labeling 23j ^ _f which has advantageous properties for use in nuclear medicine and which za3

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Sinina lately used. These properties are short half-life, low radiation exposure of the patient and suitable radiation energy for detection. The implementation of the kits increases the safety of the work, as it is always carried out with low activity and the preparation is carried out only when necessary.

Example

Prepare the first solution by dissolving one gram of chromatographically pure disodium tetrachlorotetraiodofluorescein in 70 ml of an aqueous solution of sodium acetate at a concentration of 4 · 10 ^-1 mol / l. After dissolution, which can be accelerated by heating, 20 ml of 4.10 ^{- 4} mol / l acetic acid are added. 1 ml of 30% hydrogen peroxide was added. The pH of this solution is adjusted to 5.0 with sodium acetate or acetic acid and the solution is diluted to 100 ml. The first solution thus prepared is filtered by millipore filtration and filled in one ml in 10 ml containers. A second solution is prepared by adding 0.65 g of sodium hydroxide, 50 mg of anhydrous sodium dihydrogen phosphate and 3.3 mg of chelatone III to 500 ml of water for injection. After dissolution and dilution to a volume of 800 ml, the solution is filtered by millipore filtration. The second solution thus prepared is filled in 8 ml in 10 ml containers. To the vial containing the first solution was added 40 MBq of sodium iodide radioactive solution - Na 2 - via syringe through a stopper. After shaking, the vial is immersed for 30 min. into a boiling water bath. The entire volume of the container containing the second solution is then added via syringe. After shaking, the preparation is ready for use.

Claims (1)

A method for producing the injection solution of Rose Bengal radiolabeled iodine used in nuclear medicine for functional tests and liver imaging, characterized in that to the previously prepared non-radioactive reaction mixture consisting of a solution tetrachlorotetrajodofluoresóeinu concentration of 10 * ^ to 10 ^- ^ mol / 1 acetate buffer pH 4 to S and the hydrogen peroxide concentration of 10 ^- ^ to 1 mol / 1 was added 10-500 LIBq radioactive sodium iodide solution and the resulting solution optionally after heating to a temperature of 50-100 ° C, mixed in a 1 : 5 to 1:20 with a second preformed solution containing non-radioactive sodium dihydrogen phosphate at a concentration of 10 to 10 mol / 1, and optionally complexone 3 at a concentration of 10 to 10 mole ^-D / 1st