Sorbent for receiving radionuclide arsenic-72, production of this sorbent and its use

Description

Technical Field

[0001] The invention subject is the way of obtaining a radioactive isotope of arsenic-72 of a high radionuclide purity, forming in the course of a decomposition of parent selenium-72, as well as the sorbent and the way of its production, with the use of hydrophobic styrene-divinylbenzene copolymers. According to the invention, obtaining a radionuclide pure isotope consists in its selective separation from the parent radionuclide, forming at nuclear reactions.

Background Art

[0002] Radionuclide ⁷²As is an isotope of potential use in positron emission tomography (PET) diagnostics. It is an isotope of a relatively long half-life (T_1/2=1,08 day), thanks to which it can be used for examination and observation of biochemical processes, characterised by a slow reaction kinetics. Compounds marked with ⁷²As are potential radiopharmaceuticals for receptor diagnostics and research and tracing physiological and metabolic processes.

[0003] One of known methods of obtaining ⁷²As is production in a cyclotron in a nuclear reaction: ⁷²Ge(p,n)⁷²As. An alternative way is obtaining this isotope using the generating method by the means of separating ⁷²As from the parent isotope ⁷²Se.

[0004] Obtaining ⁷²As from the generator ⁷²Se/⁷²As seems to be especially essential for centres and hospitals which do not posses own cyclotrons, as well as for entities located in far distances from functioning cyclotrons.

[0005] During last year's, several works were published, which confirm the interest in arsenic isotopes and possibilities of using them at PET examinations [C. Le Loirec, C. Champion, Track structure simulation for positron emitters of physical interest. Part III: The case of the non-standard radionuclides. Nuclear Instruments and methods in Physics Research A, 582 (2007), 665-672].

[0006] Subject references on ⁷²Se/⁷²As generators are quite scanty. First works on a selenium-arsenic generator were started over 30 years ago [S. H. Al. -Kourashi, G. G. J. Boswell, An isotope generator for 72As, Int. J. Appl. Radiat. lsot. 29 (1978), 607-609]. Various approaches were used - from holding selenium coagulates up on ionite columns and eluting ⁷²As [S. H. Al.-Kourashi, G. G. J. Boswell, An isotope generator for 72As, Int. J. Appl. Radiat. lsot. 29 (1978), 607-609], through electrolytic embedding selenium on a platinum electrode in the form of Cu⁷²Se [D. R. Phillips, V. T. Hamilton, M. D. Taylor, J. E. Farnham, A. M. Emran, R. W. Rowe, D. Pattel, Generator- produced arsenic-72 in positron emission tomography, Radioac. Radiochem. 3 (1992), 53-58], up to generators in which ⁷²As is extracted by the means of distillation of volatile AsCl₃, while ⁷²Se remains in non-volatile leavings [M. Jennewein, A. Schmidt, A. F. Novgorodov, S. M. Qaim, F. Rösch, A no-carrier-added 72Se/72As radionuclide generator based on distillation, Radiochimica Acta, 92 (2004), 245-249]. In case of a generator based on distillation of ⁷²AsCl₃, the efficiency of ⁷²As recovery is over 99% at properly selected process conditions. However, radionuclide purity of the obtained isotope depends of the distillation time - the longer process, the higher content of ⁷²Se in the arsenic fraction. What is more, in case of such generator, the arrangement is quite complex and difficult to be automated [M. Jennewein, A. Schmidt, A. F. Novgorodov, S. M. Qaim, F. Rösch, A no-carrier-added 72Se/72As radionuclide generator based on distillation, Radiochimica Acta, 92 (2004), 245-249]. In 2005, a publication was issued, in which a traditional column generator was proposed, where selenium-72 is held-up on polystyrene sorbent. Depending on the used eluent, efficiency of ⁷²As elution is not higher than 60%; in each case, also the held-up selenium is eluted (up to 2% in discharge) [M. Jennewein, S. M. Qaim, P. V. Kulkarni, R. P. Mason, A. Hermanne, F. Rösch, A no-carrier-added 72Se/72As radionuclide generator based on solid phase extraction, Radiochimica Acta, 93 (2005), 579-583].

[0007] In none of known ways of producing arsenic-72 radionuclide, especially in none of known ways of extracting arsenic radionuclide from selenium radionuclide, extraction chromatography has not yet been used.

[0008] Unexpectedly, it turned out that it is possible to obtain arsenic-72 radionuclide, using hydrophobic styrene-divinylbenzene copolymers as sorbents, with embedded especially selected aromatic ortho-diamines, according to the invention.

Summary of invention

[0009] According to the invention, the method of obtaining arsenic-72 radionuclide from selenium-72 radionuclide, consists in separating arsenic radionuclide from selenium radionuclide by the means of extraction chromatography, using hydrophobic styrene-divinylbenzene copolymers, especially Amberlite XAD-4 or Bio-Beads SM-2 carriers, with embedded substance, from the group of aromatic ortho-diamines, favourably 3,3' diaminobenzidine or 2,3 naphthalenediamine.

[0010] The invention method, consists in placing 0.1-1 mL of Se-72 solution, containing selenium in the quartic level of oxidation on a glass column of 3-5 mm diameter and 35-55 mm height, containing sorbent with embedded, especially selected aromatic ortho-diamine, in the proportion of R-0.15, of grains diameter from 0.1 to 2 mm, and next, using 5 ml of hydrous solution of hydrochloric acid or sodium chloride, arsenic-72 radionuclide is eluted from the bed.

[0011] According to the invention, elution of ⁷²As radionuclide is conducted in a temperature close to room temperature, ±10°C.

[0012] Favourably, according to the invention, for the aims of separating arsenic ions from selenium ions, hydrophobic styrene-divinylbenzene copolymer, with embedded aromatic ortho-diamine, at the proportion R-0.15, is used.

[0013] According to the invention, the sorbent for obtaining arseninc-72 radionuclide, is characterised by the fact that it is a carrier in the form of hydrophobic styrene-divinylbenzene copolymer, favourably Amberlite XAD-4 or Bio-Beads SM-2 carrier, with embedded substance from the group including aromatic ortho-diamines, favourably 3,3' diaminobenzidine or 2,3 naphthalenediamine.

[0014] According to the invention, the way of obtaining the sorbent for production of arsenic-72 radionuclide consists in mixing aromatic ortho-diamine pre-dissolved in hydrous-alcoholic solution, especially in the proportion 1:1, with an favourable carrier selected from the group of hydrophobic styrene-divinylbenzene copolymers, especially Amberlite XAD-4 or Bio-Beads SM-2, after which, the solvent is evaporated, favourably in the temperature of about 60°C, stirring from time to time, until "arid" coloured sorbent is obtained.

[0015] According to the invention, we use the ratio of embedding carrier with properly selected aromatic ortho-diamine, i.e. R= m _{aromatic ortho-diamnine}/m hydrophobic styrene-divinylbenzene copolymer =0.15. Ortho-diamines form with selenium (IV) a solid, hardly-soluble piazoselenol complex, not sorbing arsenic ions. Taking the above mentioned features into consideration, it was decided to prepare the sorbent, embedding properly selected aromatic ortho-diamines on hydrophobic styrene-divinylbenzene carrier and use it for separating arsenic radionuclide from selenium radionuclide.

[0016] According to the invention, arsenic-72 radionuclide is separated from its parent selenium-72 isotope in the way consisting in embedding selenium-72 radionuclide in the form of a hydrous hydrochloric acid and in the form of Se(IV) on the glass column filled with the prepared sorbent, pre-balanced with 0.1 M hydrochloric acid. Favourably, the diameter of bed grains ranges from 0.1 to 0.5 mm, depending on the column dimensions. Column dimensions and bed amount depend on the amount of embedded parent radionuclide. Next, ⁷²As radionuclide is eluted using hydrous solution of hydrochloric acid or hydrous solution of sodium chloride. Radionuclides elution is conducted at normal conditions, i.e. room temperature, but also higher and lower temperatures are permitted as well.

[0017] One advantage of the invention solution is the possibility to obtain high activity of the carrier-free ⁷²As isotope of high radionuclide purity from a radionuclide generator, according to a fast, single-stage separation procedure. Additionally, there is the possibility of direct obtaining radioactive preparations in the form of pure hydrous solutions of hydrochloric acid or sodium chloride solutions, not containing any complexing substances, nor any other impurities.

[0018] Below examples illustrate the way according to the invention:

Description of embodiments

Example I:

[0019] A glass column, with diameter of 4 mm and height of 50 mm, was filled with the following bed: Amberlite XAD-4- 3,3'-diaminobenzidine in the proportion of R=0.15 and diameter of grains of 0.1-0.2 mm. Next, the column was rinsed with 25 mL of 0.1 M HCI solution. 500 µl of carrier-free ⁷²Se (in the form of Se(IV)) was placed on the column front. As-72 was eluted from the column using 10 mL of 0.1 M solution of hydrochloric acid. The radionuclide purity of the obtained ⁷²As preparation was over 99.9 %

Example II:

[0020] A glass column, with diameter of 4 mm and height of 50 mm, was filled with the following bed: Amberlite XAD-4- 3,3'-diaminobenzidine in the proportion of R=0.15 and diameter of grains of 0.1-0.2 mm. Next, the column was rinsed with 25 mL of 0.1 M HCl solution. 500 µl of carrier-free ⁷²Se (in the form of Se(IV)) was placed on the column front. ⁷²As was eluted from the column using 10 mL of 0.9% solution of sodium chloride (physiological saline). The radionuclide purity of the obtained ⁷²As preparation was over 99.9 %

Example III:

[0021] A glass column, with diameter of 4 mm and height of 50 mm, was filled with the following bed: Bio-Beads SM-2 -2,3- naphthalenediamine, in the proportion of R=0.15 and diameter of grains of 0.1-0.2 mm. Next, the column was rinsed with 25 mL of 0.1 M HCl solution. 500 µl of carrier-free ⁷²Se (in the form of Se(IV)) was placed on the column front. ⁷²As was eluted from the column using 10 mL of solution of hydrochloric acid. The radionuclide purity of the obtained ⁷²As preparation was over 99.9 %

Example IV:

[0022] A glass column, with diameter of 4 mm and height of 50 mm, was filled with the following bed: Bio-Beads SM-2 -2,3- naphthalenediamine, in the proportion of R=0.15 and diameter of grains of 0.1-0.2 mm. Next, the column was rinsed with 25 mL of 0.1 M HCl solution. 500 µl of carrier-free ⁷²Se (in the form of Se(IV)) was placed on the column front. ⁷²As was eluted from the column using 10 mL of 0.9% solution of sodium chloride (physiological saline). The radionuclide purity of the obtained ⁷²As preparation was over 99.9 %

Claims

1. A method of obtaining arsenic-72 radionuclide from selenium-72 radionuclide, consisting of separating the arsenic radionuclide from the selenium radionuclide by means of extraction chromatography, characterised by using hydrophobic styrene-divinylbenzene copolymers, especially Amberlite XAD-4 or Bio-Beads SM-2 carriers, with embedded substance, from the group of aromatic ortho-diamines, favourably 3,3' diaminobenzidine or 2,3 naphthalenediamine.

2. The method, according to claim 1, consisting of placing 0.1-1 mL of Se-72 solution, containing selenium in the quartic level of oxidation on a glass column of 3-5 mm diameter and 35-55 mm height, containing sorbent with embedded, especially selected aromatic ortho-diamine, in the proportion of R-0.15, of grains diameter from 0.1 to 2 mm, and next, using 5 ml of hydrous solution of hydrochloric acid or sodium chloride, arsenic-72 radionuclide is eluted from the bed.

3. The method, according to claim 1, where elution of ⁷²As radionuclide is conducted at a temperature close to room temperature, ±10°C and for the aims of separating arsenic ions from selenium ions, hydrophobic styrene-divinylbenzene copolymer, with embedded aromatic ortho-diamine, at the proportion R-0.15, is used.

4. A sorbent for obtaining arseninc-72 radionuclide, characterised by the fact that it is a carrier in the form of hydrophobic styrene-divinylbenzene copolymer, favourably Amberlite XAD-4 or Bio-Beads SM-2 carrier, with embedded substance from the group including aromatic ortho-diamines, favourably 3,3' diaminobenzidine or 2,3 naphthalenediamine.

5. A method of obtaining the sorbent for production of arsenic-72 radionuclide consisting of mixing aromatic ortho-diamine pre-dissolved in hydrous-alcoholic solution, especially in the proportion 1:1, with an favourable carrier selected from the group of hydrophobic styrene-divinylbenzene copolymers, especially Amberlite XAD-4 or Bio-Beads SM-2, after which, the solvent is evaporated, favourably in the temperature of about 60°C, stirring from time to time, until "arid" coloured sorbent is obtained.

6. The method, according to claim 5, where the ratio of embedding carrier with properly selected aromatic ortho-diamine, i.e. R= m _{aromatic ortho-diamine}/m hydrophobic styrene-divinylbenzene copolymer =0.15.

Ansprüche

1. Verfahren zur Gewinnung von Arsen-72-Radionuklid von Selen-72-Radionuklids, besteht in der Trennung von Selen Radionuklid aus dem Arsen Radionuklid durch die Extraktionsmittel-Chromatographie, gekennzeichnet durch Verwendung von hydrophoben Styrol-Divinylbenzol-Copolymere, insbesondere Amberlite XAD-4 oder Bio-Beads SM-2 Träger, mit eingebetteten Substanz, aus der Gruppe der aromatischen ortho-Diaminen, vorteilhaft 3,3' Diaminobenzidin oder 2,3 Naphthalindiamin.

2. Verfahren nach Anspruch 1, besteht darin, indem 0,1-1 ml Se-72-Lösung, enthaltend Selen in vierter Grad der Oxidation auf eine Glassäule von 3-5 mm Durchmesser und 35-55 mm Höhe, mit einem Sorptionsmittel mit eingebetteten , insbesondere ausgewählt aromatischen ortho-Diamins, in einem Anteil von R-0,15, Durchmesser der Körner von 0,1 bis 2 mm, und als nächstes wird unter Verwendung von 5 ml wasserhaltigen Lösung von Salzsäure oder Natriumchlorid, Arsen-72-Radionuklids aus dem Bett eluiert .

3. Verfahren nach Anspruch 1, worin die Elution von ⁷²As Radionuklid in einer Temperatur nahe Raumtemperatur durchgeführt, ±10 [deg.] C und für die Ziele der Trennung von Arsen-lonen von Selenionen, hydrophoben Styrol-Divinylbenzol-Copolymer, mit eingebetteten aromatischen ortho-Diamins, bei dem Verhältnis von R-0,15, verwendet.

4. Sorbens zur Gewinnung Arsen-72 Radionuklid, dadurch gekennzeichnet, daß es ein Träger in Form von hydrophoben Styrol-Divinylbenzol-Copolymer, günstigerweise Amberlite XAD-4 oder Bio-Beads SM-2-Träger, mit eingebetteten Substanz aus der Gruppe umfassend aromatische ortho-Diamine, günstig 3,3' Diaminobenzidin oder 2,3 Naphthalindiamin.

5. Ein Verfahren zum Erhalten des Sorbens zur Herstellung von Arsen-72 Radionuklid besteht aus dem Mischen aromatischen ortho-Diamins in wasserhaltige alkoholische Lösung, insbesondere im Verhältnis 1:1 mit einer ausgewählt aus der Gruppe von hydrophoben Styrol-Divinylbenzol-Träger günstig vorgelöst Copolymere, insbesondere Amberlite XAD-4 oder Bio-Beads SM-2, wonach man das Lösungsmittel verdampft, vorteilhaft in der Temperatur von etwa 60 [deg.] C, Rühren von Zeit zu Zeit, bis "trocken" farbigen Sorbens erreicht ist.

6. Verfahren nach Anspruch 5, wobei das Verhältnis der Einbettung Träger mit richtig ausgewählten aromatischen ortho-Diamin, d.h. R = m _{aromatischen ortho-Diamin}/m hydrophoben Styrol-Divinylbenzol-Copolymer = 0,15.

Revendications

1. Procédé d'obtention de l'arsenic-72 radionucléide de sélénium-72 radionucléide, consiste à séparer radionucléide arsenic à partir de sélénium radionucléide par le moyen d'une chromatographie d'extraction, caractérisé par l'utilisation hydrophobes des copolymères de styrène-divinylbenzène, spécialement l'Amberlite XAD-4 ou Bio-Beads SM-2 des supports, avec la substance incorporée, dans le groupe de orto-diamines aromatiques, avantageusement le 3,3' diaminobenzidine ou 2,3 naphtalènediamine.

2. Procédé, selon la revendication 1, consiste à placer de 0,1 à 1 mL de solution de Se-72, contenant du sélénium dans le niveau du quatrième degré de l'oxydation sur une colonne de verre de diamètre 3 à 5 mm et de 35 à 55 mm de hauteur, contenant un agent de sorption avec embarqué , en particulier choisi orto-diamine aromatique, de la proportion de R-0,15, d'un diamètre de grains de 0,1 à 2 mm, et ensuite, en utilisant 5 ml d'une solution hydratée d'acide chlorhydrique ou du chlorure de sodium, l'arsenic-72 radionucléide est élué à partir du lit .

3. Procédé, selon la revendication 1, où l'élution de ⁷²As radionucléide est effectuée dans une température proche de la température ambiante, ±10 [deg.] C et pour les objectifs de la séparation des ions d'arsenic à partir d'ions de sélénium, un copolymère styrène-divinylbenzène hydrophobe, avec orto-diamine aromatique, incorporé à la proportion de R-0.15, est utilisé.

4. Un agent de sorption pour l'obtention de l'arsenic-72 radionucléide, caractérisé par le fait qu'il s'agit d'un support sous la forme de copolymère styrène-divinylbenzène hydrophobe, avantageusement de l'Amberlite XAD-4 ou Bio-Beads SM-2 support, avec la substance embarqué dans le groupe comprenant aromatique Orto-diamines, favorablement 3,3' diaminobenzidine ou 2,3 naphtalènediamine.

5. Procédé d'obtention de l'agent de sorption pour la production de l'arsenic-72 radionucléide consiste à mélanger orto-diamine aromatique pré-hydraté dissous dans une solution alcoolique, en particulier dans la proportion de 1:1, avec un support favorable choisi dans le groupe hydrophobe de styrène-divinylbenzène copolymères, spécialement l'Amberlite XAD-4 ou Bio-Beads SM-2, après quoi, le solvant est évaporé, de manière favorable à la température d'environ 60 [deg.] C, en remuant de temps en temps, jusqu'à ce que "aride" coloré absorbant est obtenu.

6. Procédé, selon la revendication 5, dans laquelle le rapport de porteuse avec enrobage orto-diamine aromatique convenablement choisi, c'est à dire R = m aromatique orto-diamine/m un copolymère styrène-divinylbenzène hydrophobe = 0,15.