CS249289B1 - A method for producing a solution of bromosulfaleine labeled with radioactive isotope of iodine - Google Patents

Abstract

The solution relates to a method for producing an injection solution of bromsulfalein labeled with a radioactive iodine isotope. The essence of the invention is that a previously prepared reaction mixture consisting of chromatographically pure bromsulfalein in an aqueous solution with a concentration of 10”^· to 10“4 mol/l and a pH value of 2.0 to 8.0 and hydrogen peroxide with a concentration of 10”^ to 10_3 mol/ /l is treated with a solution of 50-2,000 MBq of radioactive sodium iodide Na12^I or sodium iodide Na^25j or sodium iodide Na^li and the resulting solution, after heating to a temperature of 80 to 120 °C, is mixed in a ratio of 1:5 to 1:20 with a second prepared non-radioactive solution containing sodium dihydrogen phosphate with a concentration of 10”^ to 10“^ mol/l and complexone 3 with a concentration of 10~2 to 10“6 mol/ /l. The solution can be applied to radiopharmaceutical manufacturers and nuclear medicine departments.

Description

The present invention provides a method for the preparation of an injectable solution of radiolabelled iodine bromosulfalein used in nuclear medicine for the functional examination of the liver.

Iodine-labeled bromosulfalein (disodium salt of 4, 5, 6, 7-tetrabromophthalein-3,3'-disulfonic acid) is most commonly prepared by iodination of a non-radioactive substance using iodine chloride labeled with an iodine labeled in an acidic environment. It is sometimes iodinated in boiling methanol, as opposed to iodination in water. Iodination of bromosulfalein with radioactive iodine with hydrogen peroxide or chloramine T and electrolytic iodination was also tested, but the yields did not reach the level of iodine chloride iodination with hydrogen peroxide labeling up to a maximum of 89%.

A common drawback of all the above methods is the fact that there is no uniform and defined product. Opinions on the composition of the labeled bromosulfalein vary, it is said that the bromine atom appears to be replaced by iodine. Some sources refer to the composition of the preparation as a mixture of mono-iodo-bromosulfalein and di-iodo-bromosulfalein, whose ratio can be controlled by the choice of reaction conditions, but which are always present in the formulation, only with a large excess of iodinating agent.

Hitherto commercially produced preparations thus contain, as a predominant component, unreacted bromosulfalein and, in some proportions, mono- and diiodo-bromosulfalein. At the same time, the biological behavior of the individual components is different and therefore it is necessary to prepare labeled diiodobromosulfalein by means of an isotopic exchange reaction in high radiochemical purity.

For some purposes, especially functional tests, it is preferable to use mono iodobromosulfalein, which has a faster elimination rate from the body. These disadvantages are overcome by the process according to the invention. The preparation of an iodine-labeled bromosulfalein injectable solution is carried out here by treating a pre-prepared non-radioactive reaction mixture consisting of chromatographically pure bromosulfalein in an aqueous solution having a concentration of 10 to 10 ^-4 mol / l and a pH of 2.0 to 8.0 and hydrogen peroxide concentration of 10 ¹ to 10 mol / 1 with a solution of 50-2 000 MBq of radioactive sodium iodide at ¹²³ £ ι no> of sodium iodide, Na ⁴³³ I or Na ¹³¹ sodium iodide I and thus the resulting solution, after warming to 80 up to 120 ° C mixed in proportion

1: 5 to 1:20 with a second prepared non-radioactive solution containing dihydrogen phosphate

-2-6 -2-6 sodium at a concentration of 10 to 10 mol / l and complexone 3 at a concentration of 10 to 10 mol / l.

The process described provides a uniform product in a short time in high yield. This makes it possible to prepare the product in a simple manner from a pre-prepared reaction mixture which can be stored for several months. This is particularly advantageous in the preparation of the isotope-labeled ⁴²³ I preparation, which has a short half-life (13 hours) and where labeling needs to be done quickly and in high yield. The process according to the invention is also more suitable from the viewpoint of radiation safety, since, unlike the prior art, radioactive elemental iodine, which easily forms aerosols, is not used.

Example 1

Κ 1 ml of 10 M solution of chromatographically pure bromosulfalein in 0.2 M acetate buffer, pH 5.0, add 0.2 ml of sodium iodide Na ¹³¹ L, heat on a boiling water bath for 4 minutes, add 0.1 ml of 3% hydrogen peroxide and continue heating on a water bath for an additional 10 minutes. The mixture thus obtained is made up into the final dosage form by adding 9 ml of a solution containing 10 ^-4 M -4 sodium dihydrogen phosphate and 10 M complexon 3.

Example 2

Proceeding as in case 1, except that the reaction mixture bromsulfaleinu hydrogen peroxide is prepared in advance and stored in the cap has a vial (penicillin factory), and that instead of sodium iodide ⁴³³ I sodium iodide Na ³²³ I, which was added via syringe through the stopper. The reaction mixture thus formed is heated directly in a penicillin on a water bath.

Correction to the final dosage form is performed as in Example 1.

The process according to the invention makes it possible to produce said preparation directly at the user's workplace. It is therefore possible to prepare it according to actual needs and it is not necessary to keep it in stock. Its ready-to-use preparation according to the invention enables labeling with short-lived iodine radionuclides.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of an injectable solution of radiolabelled iodine bromosulfalein, characterized in that a pre-prepared non-radioactive reaction mixture consisting of chromium-1-matographically pure bromosulfalein in an aqueous solution having a concentration of 10 to 10 mol / l and -1 -3 pH value 2.0 to 8.0 and hydrogen peroxide at a concentration of 10 to 10 mol / l are treated with a solution of 50-2,000 MBq of radioactive sodium iodide Na ¹²³ I or a solution of sodium iodide Na ¹²⁵ I or a solution of sodium iodide Na ¹³¹ I and after heating at 80 to 120 ° C are mixed in a ratio of 1: 5 to 1:20 with a second solution containing the prepared non-radioactive 2-dihydro -6 -2 dihydrogen sodium concentration of 10 to 10 mol / 1 and the complexone 3 at a concentration of 10 ^- up 10 ^{_ €} mol / l.