CN1138008C - A preparation process of radioactive isotope gallium-67 - Google Patents

Abstract

A preparation process of radioactive isotope gallium- ^67Ga ( ^67Ga ), which relates to the separation and purification process of radioactive isotope ^67Ga produced by cyclotron. The process is characterized in that an oxidant, hydrogen peroxide ( _H2O2 ) solution, which will not affect the separation process, is added to the concentrated hydrochloric acid in which the zinc target bombarded by proton beam is dissolved, so that the low-valent gallium-67 ( ^{67Ga1 +} , ^67Ga2 ₊ ) ions in the target solution are oxidized to trivalent ions ( ^{67Ga3 +} ), ^and after evaporation, a hydrochloric acid solution of stannous chloride ( _SnCl2 ) is added to dissolve again to reduce the impurity iron ions (Fe3 ⁺ ), and then the _cation exchange column is applied to separate and purify ^67Ga . The present invention adopts the addition of two reagents, _H2O2 and _SnCl2 , to obtain a high yield (95%) of ^67Ga separation and high quality of purification (the impurity iron content is less than 5μg/mL-5mCi- ^67Ga ). This ensures that the content of impure iron in the tumor imaging agent gallium citrate produced by using ⁶⁷ Ga in nuclear medicine is as low as possible.

Description

A Preparation Technology of Radioactive Isotope Gallium-67

1. Technical field

The invention belongs to the technical field of radioisotope preparation, in particular to a separation and purification process of gallium-67 radioisotope produced by bombarding a zinc-68 target with protons accelerated by a cyclotron.

2. Background technology

⁶⁷ Ga is an important nuclide in nuclear medicine. The gallium citrate prepared from it can be concentrated in many cancerous tumor tissues. Early diagnosis and identification are of great significance. Therefore, this radioisotope has been researched and applied in the field of nuclear medicine as early as the 1970s.

There are many chemical separation methods for gallium-67, mainly divided into organic solvent extraction and ion exchange. There are also many organic solvents used to extract gallium-67 radioactive isotope. The main disadvantage of this method is that the radioactive organic solution produced is not easy to handle, and it is not good for the organic solvent to enter the human body, and solvent extraction is not easy to remove impurity iron, and according to It has been reported in the literature that impurity iron will make the tumor image of the gallium-67 imaging agent unclear; the ion exchange method is divided into cation exchange and anion exchange methods. Since the anion column needs to use different acidities to resolve different impurities, the so-called gradient elution, Make the process more complicated, relatively, the cation exchange process is simpler and faster. The literature Production of ⁶⁷ Ga at The OSLO Cyclotron OUP-Report 83-1 reported the process of separating ⁶⁷ Ga from the concentrated hydrochloric acid solution of the zinc target by cation exchange method, and using NaI as the reducing agent to remove impurity iron (Fe ³⁺ ), However, after repeating the process, the yield of the product is only 50-60%. It is found that ^{the 67} Ga adsorbed on the cationic resin is difficult to desorb, and the tailing phenomenon of the product is serious. If it is eluted at intervals of one day, 10% of ^{67 Ga} can be recovered. Ga, switch to Dowex-50 resin and complexing agent elution method, the effect is not satisfactory.

The method for removing impurity iron in the separation of ⁶⁷ Ga is to firstly reduce the Fe ³⁺ in the solution to Fe ²⁺ , so that it can be easily removed. There are three main reducing agents used in the literature for reducing Fe ³⁺ , namely TiCl ₃ , KI or NaI and ascorbic acid (Vc), but the results have been proved to be unsatisfactory; using TiCl ₃ as the reducing agent method, Ti ³⁺ is reduced When Fe ³⁺ becomes Ti ⁴⁺ , this ion is easily hydrolyzed into hydrated titanium oxide precipitation at low acidity, and forms a thin layer of shell on the outer surface of the resin, which makes the resin lose its ion exchange capacity, that is, "resin poisoning", affecting ^{67 The} product quality and yield of Ga, the effect that makes resin regeneration use at the same time is bad ^; The potential (0.771V) is relatively close, so the reduction of ferric ions (Fe ³⁺ ) is slow and the effect is poor. At the same time, iodine molecules (I ₂ ) are generated during reduction, which are difficult to remove in the product and affect the color of the product; As for the use of ascorbic acid (VC), it is not easy to separate due to its instability and low solubility.

3. Contents of the invention

The present invention realizes by implementing following scheme:

A preparation process of the radioactive isotope gallium-67 ( ⁶⁷ Ga), including bombarding a zinc target ( ⁶⁸ Zn) with protons accelerated by a cyclotron, and generating ⁶⁷ Ga through a (p, 2n) reaction, which is dissolved in concentrated hydrochloric acid Add a reducing agent to reduce impurity iron ions (Fe ³⁺ ), and then use the cation exchange method to separate and purify ⁶⁷ Ga from the concentrated hydrochloric acid solution of the zinc target. The specific process steps are as follows:

(1) Add the oxidant hydrogen peroxide to the concentrated hydrochloric acid as the target solution to make the target solution

Low-priced gallium-67 ( ⁶⁷ Ga ¹⁺ , ⁶⁷ Ga ²⁺ ) ions are oxidized to trivalent ions

( ⁶⁷ Ga ³⁺ ), after dissolving the target, slowly evaporate the solution to dryness with a warm fire at 80-90°C,

remove H ₂ O ₂ ;

(2) redissolve the above-mentioned solution with the hydrochloric acid solution of _SnCl2 , then go up cationic column,

The concentration of hydrochloric acid is 7mol/L;

(3) wash the impurities on the column with hydrochloric acid solution of _SnCl2 and 7mol/L hydrochloric acid respectively

Nuclide zinc, iron, copper, etc.;

(4) Finally, gallium-67 was eluted with 3.5 mol/L hydrochloric acid.

Wherein, the volume ratio of the added amount of hydrogen peroxide to concentrated hydrochloric acid is 1:3-1:4, and the concentration of hydrogen peroxide can be 30%.

In addition, the _SnCl concentration in the hydrochloric acid added during the secondary target dissolution in step (2) is 5 mg/mL, and _the SnCl concentration used when washing the impurities on the column in step (3) is 50 mg/mL.

The principle of the present invention will be described below.

Since metal gallium (atom) ⁶⁷ Ga forms gallium ions in three valence states of ⁶⁷ Ga ¹⁺ , ⁶⁷ Ga ²⁺ and ⁶⁷ Ga ³⁺ when it dissolves, gallium ions in different valence states have different chemical behaviors. Ions ( ⁶⁷ Ga ¹⁺ , Ga ₂ ²⁺ ) are unstable and easy to oxidize, Ga ³⁺ is the most stable oxidation state of gallium, and hydrogen peroxide (H ₂ O ₂ ) has a higher oxidation-reduction standard potential, E ₀ ＝+1.77V, based on the above reasons, it is considered that the reactions of the following two formulas are established and existing in the zinc target solution, that is,

(1)

(2) Therefore, the present invention adds hydrogen peroxide to the concentrated hydrochloric acid that dissolves the zinc target, so that the less stable low-valence gallium, i.e. monovalent gallium, and divalent gallium are oxidized into the most stable single valence state, i.e. trivalent gallium ions, and then cation exchange to separate and purify gallium. The results show that ^{the 67} Ga adsorbed on the cation resin is difficult to desorb, that is, the phenomenon of product tailing occurs, and the product yield of gallium is over 95%.

Regarding the removal of impurity Fe3 ⁺ , because some methods disclosed in the literature have such and such defects, the present invention considers that it will be nontoxic and harmless to the human body from the nuclides that may react in the oxidation-reduction potential value, and selects SnCl ₂ , a commonly used reducing agent in organic biochemical reactions, results show that it reduces Fe ³⁺ more thoroughly, and is easy to be removed, so that the impurity iron in the product is less than 5 μg/mL (the concentration of ⁶⁷ Ga is 5mCi /mL), to ensure the high quality of the product.

4. Specific implementation

Example of process steps for separating and purifying gallium-67 in zinc target:

(1) 900 mg of zinc target, use 10 mL of concentrated hydrochloric acid, add 3 mL of 30% hydrogen peroxide as the target solution, after dissolving the target, slowly evaporate to dryness at 90°C to remove H ₂ O ₂ ;

(2) After dissolving the above solution with 20ml SnCl ₂ (concentration is 5mg/ml) hydrochloric acid (concentration is 7mol/L) solution, put on the cation exchange column;

(3) with 20mL _SnCl2 (concentration is 50mg/ml) hydrochloric acid (concentration is 7mol/L) solution and 50mL concentration is the hydrochloric acid solution of 7mol/L respectively to rinse impurity nuclide Zn, Fe and Cu etc. on the column;

(4) Finally, ⁶⁷ Ga was eluted with 3.5 mol/L hydrochloric acid.

Claims (4)

1. Radioisotope gallium-67 (⁶⁷A process for the preparation of Ga) which comprises bombarding a zinc target with protons accelerated by a cyclotron⁶⁸Zn) by a (p, 2n) reaction to form⁶⁷Ga, adding reduced impurity iron ion (Fe) into concentrated hydrochloric acid for dissolving target³⁺) Then separating and purifying the reducing agent from the concentrated hydrochloric acid solution of the zinc target by a cation exchange method⁶⁷Ga, characterized in that: the specific process steps are as follows:

(1) adding oxidant hydrogen peroxide into concentrated hydrochloric acid as target dissolving solution

Low valence gallium-67 (⁶⁷Ga¹⁺，⁶⁷Ga²⁺) Oxidation of ions to trivalent ions

(⁶⁷Ga³⁺) After dissolving the target, slowly evaporating the solution to dryness by using a slow fire at 80-90 ℃ to remove

Removing H₂O₂；

(2) With SnCl₂The hydrochloric acid solution redissolves the above solution, and then goes to a cation column, which

The concentration of the medium hydrochloric acid is 7 mol/L;

(3) respectively with SnCl₂Hydrochloric acid solution and 7mol/L hydrochloric acid to elute impurity nuclei on column

Elemental zinc, iron, copper, etc.;

(4) finally, eluting gallium-67 by using 3.5mol/L hydrochloric acid.

2. The process according to claim 1, wherein the volume ratio of the hydrogen peroxide to the concentrated hydrochloric acid is 1: 3 to 1: 4.

3. The process according to claim 1, wherein SnCl in hydrochloric acid is added during the second target dissolving in step (2)₂The concentration of (2) is 5 mg/mL.

4. The process according to claim 1, wherein SnCl used in the eluting of impurities on the column in the step (3)₂The concentration of (3) is 50 mg/mL.