CS249288B1 - A method for producing a solution of bromosulfaine labeled with radioactive isotope of iodine - Google Patents

Abstract

The solution relates to a method of producing an injectable solution of bromsulfalein labeled with a radioactive iodine isotope. The essence of the solution is that a previously prepared reaction mixture consisting of chromatographically pure monoiodobromosulfalein in an aqueous solution with a concentration of 10"! to 10"4 mol/1 with a pH value of 2.0 to 8.0 and copper chloride with a concentration of 10"2 to 10-5 mol/1 is treated with a solution of 50 to 2,000 MBq of radioactive sodium iodide Na 123j or sodium iodide Na 125j or sodium iodide Na 131I 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 10~2 to 10"® mol/1 and complexone 3 with a concentration of 10-3 to 10-6 mol/1. The essence of the solution can be applied to radiopharmaceutical manufacturers or nuclear medicine departments.

Description

(54) A method for producing an iodine-labeled bromosulfainine solution for injection

The present invention relates to a process for the preparation of an injectable solution of radiolabelled iodine bromosulfain. The essence of the solution is that for a pre-prepared reaction mixture consisting of chromatographically pure mono iodo-bromosulfalein in an aqueous solution with a concentration of 10! ⁴ to 10 mol / 1, pH 2.0 to 8.0 and cuprous chloride at a concentration of 10 <-2 to ^10-5 mol / 1 was treated with a solution of 50 to 2000 MBq of radioactive sodium iodide or sodium iodide 123j 125j or Na sodium iodide Na ¹³¹ L and the solution thus obtained are mixed, after heating to a temperature of 80 to 120 ° C, in a ratio of 1: 5 to 1:20, with a second prepared non-radioactive solution containing sodium dihydrogen phosphate at a concentration of 10 -2 to 10 complexone 3 at a concentration of 10 ^-3 to 10 ^-6 mol / l. The essence of the solution can be applied at manufacturers of radiopharmaceuticals, or at the departments of nuclear medicine.

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.

The radioactive isotope-labeled iodine bromide sulfalein (disodium salt of 4, 5, 6, 7-tetrabromophthalein-3,3-disulfonic acid) is most commonly prepared by the iodination of a non-radioactive substance using iodine chloride labeled with the radioactive iodine in an acidic environment.

A reaction is known in which iodine is boiled in boiling methanol as opposed to iodine 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 same level as iodine chloride iodination with a maximum hydrogen peroxide labeling of 89%.

A common disadvantage of all the above methods is that there is no uniform and defined product. Opinions on the composition of labeled bromosulfalein vary. It is reported, for example, that the bromine atom in the bromosulfalein molecule is apparently exchanged for iodine, sometimes the composition of the preparation is referred to as a mixture of mono-iodobromosulfalein and diiodo-bromosulfalein, whose ratio can be controlled by choice of reaction conditions but always present in the formulation. an excess of iodinating agent produces almost exclusively the diiodo derivative.

Thus, the hitherto commercially produced preparations contain, as a predominant component, unreacted unmodified bromosulfalein and, in some proportions, mono- and diiodo-bromosulfalein. however, 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.

Accordingly, these methods are complicated by certain drawbacks that are eliminated by the process for preparing a radioactive isotope-labeled bromosulfalein injectable solution of the present invention in which a pre-prepared reaction mixture consisting of chromatographically pure mono iodobromosulfalein in an aqueous solution of 10 ⁴ to 10 ¹ mol / l and pH 2.0 to 8.0 and cuprous chloride at a concentration of 10 to 10 mol ^_ / 1 with a solution of 50-2 000 MBq of radioactive sodium iodide ^{11! 1L} or sodium iodide ^^ Si or sodium iodide to ^111! and after heating to 80 to 120 ° C, the solution is mixed 1: 5 to 1:20 with a second prepared radioactive solution containing 10 ² to 10 ⁶ mol / "2 ^- 6 / liter sodium complex and complexone 3 with a concentration of 10 to 10 mol / l.

The method according to the invention is preferable 1 from the viewpoint of radiation safety, since, unlike the prior art, radioactive elemental iodine, which easily forms aerosols, is not used.

The procedure is suitable for a bulk manufacturer of radiopharmaceutical preparations or for the nuclear medicine department.

Example

To 0.1 ml of a 5x10 M solution of chromatographically pure mono iodo bromosulfalein in acetate buffer, pH 3, add 0.5 mg of finely divided copper chloride and heat on a glycol bath for 5 minutes so that the mixture does not evaporate. 0.1 ml of radioactive sodium iodide is then added and the mixture is heated on a water bath in a sealed bottle. After completion of the reaction, the product is filtered through a 1: 3 mixture of silver chloride and sand or silver paper saturated with silver chloride and adjusted to the final dosage form by dilution, pH adjustment and sterilization. The labeling yield is 98%.

Claims (1)

OBJECT OF THE INVENTION A process for preparing an iodine-labeled bromosulfalein solution for injection, characterized in that a pre-prepared reaction mixture consisting of a chromatograph of pure mono-iodobromosulfalein in an aqueous solution having a concentration of 10 to 10 mol / l and a pH of 2.0 -5 -2 to 8.0, and cuprous chloride at a concentration of 10 to 10 mol / 1 with a solution of 50 to 2000 MBq of radio active sodium iodide _no b _the sodium iodide NaI _not bo on L ^ lj and thus the resulting solution after heating for the temperature of 80-120 ° C is mixed in a ratio of 1: 5 to 1:20 with a second prepared non-radioactive solution containing 10-10 mol / l sodium dihydrogen phosphate and 10-10 mol / l complexone 3.