JP2013210226A - Method for manufacturing 99mtc - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for refiningTc for reducing the residual amounts of a solvent to be used in a refining process, and for improving a yield.SOLUTION: A refining method ofTc includes: a dissolution process of dissolving and pH-adjustingMo/Tc target 10 to obtain an alkaline solution; an anion-exchange column absorption process of introducing the solution to an anion-exchange column 13 to absorbMo andTc; aMo removal process of removing the absorbedMo with the solution; aTc extraction process of extracting the absorbedTc with the solution; aTc solution preparation process of drying and solidifying extract, and adding water to obtain aTc solution; an acid alumina column absorption process of introducing the solution containingTc to an acid alumina column 15 to make the acid alumina column 15 absorbTc; and aTc recovery process of extracting and recoveringTc absorbed by the acid alumina column 15 with a saline solution.

Description

The present invention relates to a ^99m Tc purification method for purifying ^99m Tc from a ⁹⁹ Mo / ^99m Tc target.

Conventionally, a ^99m Tc purification method described in Non-Patent Document 1 below is known as a technique in such a field. This purification method is as follows. First, ⁹⁹ Mo / ^99m Tc target is dissolved with an H ₂ O ₂ solution or the like to obtain a solution having a pH of ₂ to 3 (step a). When this solution is introduced into the anion exchange column, ⁹⁹ Mo and ^99m Tc are collected in the anion exchange column (step b). Thereafter, an aqueous NaCl solution is introduced into the anion exchange column, and ⁹⁹ Mo is desorbed and removed from the column (step c). Thereafter, TBAB / CH ₂ Cl ₂ is introduced into the anion exchange column to obtain a ^99m Tc solution desorbed from the anion exchange column (step d). Thereafter, when this solution is introduced into an alumina column, ^99m Tc is adsorbed onto the alumina column (step e). Thereafter, when physiological saline is introduced into the alumina column, a ^99m Tc solution desorbed from the acidic alumina column is finally obtained (step f).

Sankha Chattopadhyay, Malay KantiDas, "A novel technique for the effective concentration of 99mTcfrom a large alumina column loaded with law specific-actovity (n, γ) -produced 99Mo", Applied Radiation and Isotopes, ELSEVIER, 2008, 66, p.1295 -1299

However, in the purification method described above, the CH ₂ Cl ₂ (dichloromethane) used in step d above remains slightly in the final product ^99m Tc solution. In particular, when the finally obtained ^99m Tc is used as a radiopharmaceutical, the residual amount of an organic solvent such as CH ₂ Cl ₂ is desired to be as small as possible. In this type of purification method, it is also desired to improve the yield of ^99m Tc.

Accordingly, an object of the present invention is to provide a method for purifying ^99m Tc that can reduce the residual amount of the solvent used in the purification process and improve the yield.

Purification method of ^99m Tc of the present invention, a melting step of obtaining a method of purifying a ^99m Tc purifying the ^99m Tc from ⁹⁹ Mo / ^99m Tc target solution by dissolving the ⁹⁹ Mo / ^99m Tc target, removing the solution and an anion exchange column adsorption step a of adsorbing and introduced to an anion exchange column wherein the anion exchange column ⁹⁹ Mo and ^99m Tc, and the ⁹⁹ Mo adsorbed on the anion exchange column with a solvent ⁹⁹ Mo removal step, ^99m Tc extraction step for extracting ^99m Tc adsorbed on the anion exchange column with a solvent, and ^99m Tc containing ^99m Tc by performing a predetermined treatment on the extract obtained in the ^99m Tc extraction step and ^99m Tc solution preparation step of obtaining a solution, the ^99m acidic alumina column adsorption step a of adsorbing ^99m Tc solution to the acidic alumina column and introduced into an acidic alumina column containing Tc, ^99m Tc adsorbed on the acidic alumina column Extract with salt water and collect Comprising a ^99m Tc recovery step, and the solution of the dissolving process was made alkaline, the predetermined processing in the ^99m Tc solution preparation step, after removal of the solvent by evaporation from the extract by adding water ^99m It is the process made into Tc aqueous solution.

In this purification method, the dissolution solution in the dissolution step is made alkaline, and in the anion exchange column adsorption step, this alkaline solution is introduced into the column. Thus, by making the solution introduced into the anion exchange column alkaline, the adsorption rate of ^99m Tc on the anion exchange column is improved. As a result, ^99m Tc finally obtained is increased, and the yield of ^99m Tc is improved. In this purification method, in the ^99m Tc solution preparation step, the solvent is evaporated and removed from the extract obtained in the ^99m Tc separation step, and then water is added to obtain a ^99m Tc aqueous solution. By this treatment, the solvent used in the ^99m Tc separation step is removed and replaced with water, so that the residual amount of the solvent can be reduced in the finally obtained ^99m Tc. In addition, in the acidic alumina column adsorption process, the solution to be introduced into the acidic alumina column was ^99m Tc aqueous solution, so the adsorption rate to the column was improved compared to the case of introducing ^99m Tc C ₂ H ₂ solution. ^99m Tc finally obtained is increased, and the yield of ^99m Tc is improved.

Purification method of ^99m Tc of the present invention, ⁹⁹ from Mo / ^99m Tc targets a purification method for purifying a ^99m Tc, a melting step of obtaining a solution by dissolving the ⁹⁹ Mo / ^99m Tc target, the solution And an anion exchange column adsorption step for adsorbing ⁹⁹ Mo and ^99m Tc to the anion exchange column, and a ^99m Tc acquisition step for obtaining ^99m Tc adsorbed on the anion exchange column; The solution in the dissolving step is made alkaline.

In this purification method, the dissolution solution in the dissolution step is made alkaline, and in the anion exchange column adsorption step, this alkaline solution is introduced into the column. Thus, by making the solution introduced into the anion exchange column alkaline, the adsorption rate of ^99m Tc on the anion exchange column is improved. As a result, ^99m Tc finally obtained is increased, and the yield of ^99m Tc is improved.

Purification method of ^99m Tc of the present invention, ⁹⁹ from Mo / ^99m Tc targets a purification method for purifying a ^99m Tc, separated ^99m Tc in the solvent from the column was adsorbed lysates of ⁹⁹ Mo / ^99m Tc Target A step of preparing an extracted extract, and a ^99m Tc solution preparation step for obtaining a solution containing ^99m Tc by subjecting the extract to a predetermined treatment, and the predetermined treatment in the ^99m Tc solution preparation step is performed from the extract solution. The method is characterized in that after removing the solvent by evaporation, water is added to obtain an aqueous solution containing ^99m Tc.

In this purification method, in the ^99m Tc solution preparation step, after removing the solvent from the extract by evaporation, water is added to obtain an aqueous solution containing ^99m Tc. By this treatment, the solvent contained in the extract is removed and replaced with water, so that the residual amount of the solvent can be reduced in the finally obtained ^99m Tc.

According to the present invention, it is possible to provide a ^99m Tc purification method capable of reducing the residual amount of solvent used in the purification process and improving the yield.

It is a figure which shows each process of the purification method which concerns on one Embodiment of this invention in order. It is a figure which shows each process of the purification method which concerns on one Embodiment of this invention in order. It is a figure which shows each process of the purification method which concerns on one Embodiment of this invention in order. It is a table | surface which shows the isolation | separation conditions and isolation | separation purification efficiency of Experiment 1 which the present inventors conducted. It is a table | surface which shows the isolation | separation conditions and isolation | separation purification efficiency of Experiment 2 which the present inventors conducted.

Hereinafter, an embodiment of a method for purifying ^99m Tc according to the present invention will be described in detail with reference to the drawings.

The purification method of ^99m Tc ( ^99m- technetium) according to this embodiment includes a dissolution step, an anion exchange column adsorption step, a ⁹⁹ Mo removal step, a ^99m Tc extraction step, a ^99m Tc solution preparation step, an acidic alumina column, which will be described below. Includes adsorption process and ^99m Tc recovery process.

(Dissolution process)
First, prepare a ⁹⁹ Mo / ^99m Tc target. ^{The 99} Mo / ^99m Tc target is generated, for example, by irradiating a metal Mo (molybdenum) target with a neutron beam with a cyclotron and activating a part of Mo. Next, as shown in FIG. 1A, hydrochloric acid and hydrogen peroxide solution are added and dissolved in the prepared ⁹⁹ Mo / ^99m Tc target 11. Further, an aqueous NaOH solution is added to adjust the pH of the solution. The solution should be alkaline (pH 7.0 or higher). Preferably, the pH of the solution is adjusted to pH 11 or higher. It should be noted that the concentration of the hydrogen peroxide solution can be increased because the aqueous solution of NaOH may be finally adjusted to pH 7.0 or higher by adding NaOH aqueous solution. As a result, the dissolution rate of the ⁹⁹ Mo / ^99m Tc target 11 is improved, and the time for the dissolution process can be shortened.

(Anion exchange column adsorption process)
Next, as shown in FIG. 1B, a column (anion exchange column) 13 filled with an anion exchange resin is prepared. As the anion exchange resin, for example, Dowex 1X8 manufactured by Dow Chemical Co., etc. is preferably used. The lysate obtained in the lysis step is introduced into the prepared anion exchange column 13. Then, ⁹⁹ Mo and ^99m Tc are adsorbed in the anion exchange column 13.

( ⁹⁹ Mo removal process)
Next, as shown in FIG. 1 (c), 0.9 wt% NaCl aqueous solution (physiological saline) is introduced into the anion exchange column 13 as a Mo desorption solution. Then, ⁹⁹ Mo adsorbed on the anion exchange column 13 is desorbed and removed. Here, ^99m Tc adsorbed on the anion exchange column 13 remains in the anion exchange column 13 with almost no desorption.

( ^99m Tc extraction process)
Next, as shown in FIG. 2A, TBAB (tetrabutylammonium bromide) / CH ₂ Cl ₂ is introduced into the anion exchange column 13 as a Tc desorbing solution. Then, ^99m Tc remaining in the anion exchange column 13 is extracted and discharged from the anion exchange column 13 together with CH ₂ Cl ₂ . That is, from the outlet of the anion exchange column 13, a ^99m Tc CH ₂ Cl ₂ solution is discharged as an extract. In addition, TBAB is slightly mixed in the extract. In addition, by appropriately adjusting the TBAB concentration of the solvent TBAB / CH ₂ Cl ₂ used here, the ability to desorb ^99m Tc adsorbed on the anion exchange column 13 is improved and recovered in the extract. The amount of ^99m Tc can be increased.

( ^99m Tc solution preparation process)
Next, as shown in FIG. 2B, CH ₂ Cl ₂ is evaporated and removed from the extract obtained in the ^99m Tc extraction step to dry the extract. Thereafter, water is added to the dried product to make a ^99m Tc aqueous solution. This aqueous solution contains TBAB and ^99m Tc.

(Acid alumina column adsorption process)
Next, as shown in FIG. 3A, a column (acidic alumina column) 15 filled with acidic alumina powder is prepared. As the acidic alumina powder, for example, “Alumina A” manufactured by Wako Pure Chemical Industries, Ltd. is preferably used. The prepared acidic alumina column 15, to introduce the ^99m Tc aqueous solution obtained in the above ^99m Tc solution preparation step. Then, ^99m Tc is adsorbed on the acidic alumina column 15. Here, since an aqueous solution of ^99m Tc is used, it is considered that ^99m Tc is more easily cationized and ^99m Tc is easily adsorbed to the acidic alumina column.

( ^99m Tc recovery process)
Next, as shown in FIG. 3 (b), a 0.9 wt% NaCl aqueous solution (physiological saline) is introduced into the acidic alumina column 15. Then, ^99m Tc in the acidic alumina column 15 is extracted, and finally purified ^99m Tc is recovered in a state dissolved in physiological saline.

Then, the effect by the purification method demonstrated above is demonstrated. In this purification method, the dissolution solution in the dissolution step is made alkaline, and in the anion exchange column adsorption step, this alkaline solution is introduced into the column. Thus, by making the solution introduced into the anion exchange column alkaline, the adsorption rate of ^99m Tc on the anion exchange column is improved. As a result, ^99m Tc finally obtained is increased, and the yield of ^99m Tc is improved.

In addition, in the acidic alumina column adsorption process, the solution to be introduced into the acidic alumina column was ^99m Tc aqueous solution, so the adsorption rate to the column was improved compared to the case of introducing ^99m Tc C ₂ H ₂ solution. ^99m Tc finally obtained is increased, and the yield of ^99m Tc is improved. That is, since ^99m Tc aqueous solution is used, it is considered that ^99m Tc is more easily cationized and ^99m Tc is easily adsorbed to the acidic alumina column.

In this purification method, an organic solvent such as CH ₂ Cl ₂ is used in the ^99m Tc extraction step. It is desired that this type of organic solvent used in the purification process is finally removed as much as possible. That is, since the purified ^99m Tc finally obtained is used as a radiopharmaceutical, the residual amount of an organic solvent such as CH ₂ Cl ₂ is desired to be as small as possible. In contrast, in the purification method of the present embodiment described above, in the ^99m Tc solution preparation step, CH ₂ Cl ₂ is removed from the extract by evaporation, and then water is added to form a ^99m Tc aqueous solution. Yes. By this treatment, CH ₂ Cl ₂ used in the ^99m Tc separation step is removed and replaced with water, so that the residual amount of CH ₂ Cl ₂ can be reduced in the finally obtained ^99m Tc.

  Although one embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment, and may be modified without changing the gist described in each claim.

  Subsequently, an experiment conducted by the present inventors will be described.

[Experiment 1]
In Experiment 1, ^99m Tc was purified according to the purification method of this embodiment. Then, the radioactivity of ^99m Tc before and after separation in each step was measured with a Ge detector, and the value after / before separation was expressed as “separation purification efficiency” (%). Experiment 1 includes Experiments 1-1 to 1-3 described below.

(Experiment 1-1)
In Experiment 1-1, the separation conditions in each step were as follows.
The ⁹⁹ Mo / ^99m Tc target 11 prepared in the melting process is obtained by irradiating a metal Mo target (dimensions: 20 mm × 20 mm × 1 mm, mass: 0.7 g) with cyclotron neutrons. The irradiation conditions of the neutron beam are irradiation current = 1 μA and irradiation time = 10 minutes.

In the dissolution process, 2 mL of 1N hydrochloric acid and 0.4 mL of hydrogen peroxide solution are added to the ⁹⁹ Mo / ^99m Tc target 11 to dissolve the target, and then 2 mL of 5N NaOH aqueous solution is added to bring the pH of the solution to pH 11 or higher. It was.
The anion exchange resin used in the anion exchange column adsorption step was Dowex 1X8 manufactured by Dow Chemical Co., Ltd., and 0.4 g of this anion exchange resin was filled in a container to form an anion exchange column 13. As pretreatment of the column, 5 mL of physiological saline and 5 mL of pure water were passed.
^{In the 99} Mo removal process, 3 mL of 0.9 wt% NaCl aqueous solution was used as the ⁹⁹ Mo desorption solution.
^{In the 99m} Tc extraction step, 5 mL of TBAB / CH ₂ Cl ₂ was used as the ^99m Tc desorption solution. The TBAB concentration was 0.2 mg / ml.
The acidic alumina powder used in the acidic alumina column adsorption step was “Alumina A” manufactured by Wako Pure Chemical Industries, Ltd., and 1.5 g of this acidic alumina powder was filled in a container to obtain an acidic alumina column 15.
^{In the 99m} Tc recovery step, 5 mL of 0.9 wt% NaCl aqueous solution was used.

(Experimental result 1-1)
Then, the result of Experiment 1-1 is demonstrated.
Separation and purification efficiency in the anion exchange column adsorption step was 95%. That is, in the anion exchange column adsorption step, 95% of ^99m Tc contained in the solution was adsorbed on the anion exchange column 13.
Separation and purification efficiency in the ⁹⁹ Mo removal step was 95% or more. That is, in the ⁹⁹ Mo removal step, 95% or more of ^99m Tc adsorbed on the anion exchange column 13 remained in the anion exchange column 13 without desorption.
The separation and purification efficiency in the ^99m Tc extraction step was 84%. That is, in the ^99m Tc extraction step, 84% of ^99m Tc ^remaining on the anion exchange column 13 was extracted and discharged from the anion exchange column 13 together with CH ₂ Cl ₂ .
Separation and purification efficiency in the acidic alumina column adsorption step was 95%. That is, in the acidic alumina column adsorption step, 95% of ^99m Tc in the ^99m Tc aqueous solution obtained in the ^99m Tc solution preparation step was adsorbed on the acidic alumina column 15.
Separation and purification efficiency in the ^99m Tc recovery step was 93%. That is, in the ^99m Tc recovery step, 93% of ^99m Tc adsorbed on the acidic alumina column 15 was discharged from the acidic alumina column 15 together with the physiological saline.

(Experiment 1-2 and Experiment 1-3)
Subsequently, in Experiment 1-2, the pH of the solution was adjusted to pH 7.0 by changing the amount of NaOH aqueous solution added in the dissolution step. The other separation conditions are the same as in Experiment 1-1. Similarly, Experiment 1-3 was performed while changing the pH of the solution.

  The separation conditions of Experiment 1 (Experiment 1-1 to Experiment 1-3) are collectively shown in Table 1 (FIG. 4).

[Experiment 2]
Subsequently, in order to compare with the purification method of the present embodiment, ^99m Tc was purified according to the purification method described in Non-Patent Document 1 described above in Experiment 2. Then, as in Experiment 1, the radioactivity of ^99m Tc before and after separation in each step was measured with a Ge detector, and the value after / before separation was expressed as “separation purification efficiency” (%). Experiment 2 includes Experiment 2-1 and Experiment 2-2 described below.

(Experiment 2-1)
In Experiment 2-1, the conditions for each step were as follows.
The ⁹⁹ Mo / ^99m Tc target prepared in step a is obtained by irradiating a metal Mo target (dimensions: 20 mm × 20 mm × 1 mm, mass: 0.07 g) with a cyclotron neutron beam. The irradiation conditions of the neutron beam are irradiation current = 1 μA and irradiation time = 10 minutes.
In step a, 2 mL of 1N hydrochloric acid and 0.4 mL of hydrogen peroxide are added to the ⁹⁹ Mo / ^99m Tc target to dissolve the target, and then 2 mL of 5N NaOH aqueous solution is added to adjust the pH of the solution to pH 2.0. It was.
The anion exchange resin used in step b was Dowex1X8 manufactured by Dow Chemical Co., Ltd., and 0.4 g of this anion exchange resin was filled in a container to obtain an anion exchange column. As pretreatment of the column, 5 mL of physiological saline and 5 mL of pure water were passed.
In step c, 3 mL of a 0.9 wt% NaCl aqueous solution was used.
In step d, 5 mL of TBAB / CH ₂ Cl ₂ was used. The TBAB concentration was 0.2 mg / ml.
The alumina powder used in step e is neutral alumina powder, “AluminaN” manufactured by Wako Pure Chemical Industries, Ltd., and 1.5 g of this alumina powder was filled in a container to form an alumina column.
^{In the 99m} Tc recovery step, 5 mL of 0.9 wt% NaCl aqueous solution was used.

(Experiment 2-2)
In Experiment 2-2, the conditions of each step were as follows.
The ⁹⁹ Mo / ^99m Tc target prepared in step a is obtained by irradiating a metal Mo target (dimensions: 6 mm × 6 mm × 0.1 mm, mass: 0.1627 g) with cyclotron neutrons. The irradiation conditions of the neutron beam are irradiation current = 1 μA and irradiation time = 10 minutes.
In step a, 8 mL of 1N hydrochloric acid and 1.6 mL of hydrogen peroxide solution were added to the ⁹⁹ Mo / ^99m Tc target to dissolve the target, and 2 mL of 5N NaOH aqueous solution was further added to adjust the pH of the solution to pH 11. .
The anion exchange resin used in step b was Dowex 1X8 manufactured by Dow Chemical Co., Ltd., and 0.2 g of this anion exchange resin was filled in a container to obtain an anion exchange column. As pretreatment of the column, 5 mL of physiological saline and 5 mL of pure water were passed.
In step c, 3 mL of a 0.9 wt% NaCl aqueous solution was used.
In step d, TBAB / CH ₂ Cl ₂ was introduced in a total of 15 mL in 5 mL portions. The TBAB concentration was 0.2 mg / ml.
The alumina powder used in step e is neutral alumina powder, “AluminaN” manufactured by Wako Pure Chemical Industries, Ltd., and 1.5 g of this alumina powder was filled in a container to form an alumina column.
^{In the 99m} Tc recovery step, 5 mL of 0.9 wt% NaCl aqueous solution was used.

  The separation conditions of Experiment 2 (Experiment 2-1 to Experiment 2-2) are collectively shown in Table 2 (FIG. 5).

[Consideration of experimental results]
In Experiment 2, the separation and purification efficiency in step b was 84.9% at the maximum. On the other hand, in Experiment 1, the separation and purification efficiency in the anion exchange column adsorption step was 95% or more. Therefore, by the solution to be introduced into the anion exchange column in an alkaline, improved adsorption rate ^99m Tc to the anion exchange column, as a result, the finally obtained ^99m Tc increases, the ^99m Tc It was found that the yield was improved.

  Furthermore, when Experiments 1-1 to 1-3 were compared, it was found that the separation and purification efficiency in the anion exchange column adsorption process was improved as the pH of the solution was increased. In order to obtain sufficient separation and purification efficiency, it has been found that it is particularly preferable to set the pH of the solution to pH 11 or higher.

In Experiment 2, the separation and purification efficiency in Step f was less than 10% at the maximum. That is, the adsorption rate of ^99m Tc on the alumina column is extremely low. In contrast, in Experiment 1, the separation and purification efficiency in the acidic alumina column adsorption step was 95% or more. Therefore, by using ^99m Tc aqueous solution as the solution to be introduced into the acidic alumina column, the adsorption rate to the column is improved compared to the case of introducing ^99m Tc TBAB / C ₂ H ₂ solution. It was found that the ^99m Tc obtained was increased and the yield of ^99m Tc was improved.

As described above, according to Experiments 1 and 2, the purification method of this embodiment (Purification Method of Experiment 1) yields ^99m Tc compared to the purification method of Non-Patent Document 1 (Purification Method of Experiment 2). Was found to improve.

11 ... ⁹⁹ Mo / ^99m Tc target, 13 ... anion exchange column, 15 ... acidic alumina column.

Claims (3)

^99m Tc purification method for purifying ^99m Tc from ⁹⁹ Mo / ^99m Tc target,
A dissolution step of dissolving the ⁹⁹ Mo / ^99m Tc target to obtain a solution;
An anion exchange column adsorption step for introducing the lysate into the anion exchange column and adsorbing ⁹⁹ Mo and ^99m Tc to the anion exchange column;
⁹⁹ Mo removal step of removing ⁹⁹ Mo adsorbed on the anion exchange column with a solvent;
^99m Tc extraction step of extracting ^99m Tc adsorbed on the anion exchange column with a solvent;
A ^99m Tc solution preparation step for obtaining a solution containing ^99m Tc by subjecting the extract obtained in the ^99m Tc extraction step to a predetermined treatment;
An acidic alumina column adsorption step a of adsorbing ^99m Tc solution to the acidic alumina column and introduced into an acidic alumina column containing the ^99m Tc,
^99m Tc recovery step of extracting and recovering ^99m Tc adsorbed on the acidic alumina column with saline,
Making the solution in the dissolution step alkaline,
The predetermined treatment in the ^99m Tc solution preparation step is:
A method for purifying ^99m Tc, which is a process of evaporating and removing a solvent from the extract and then adding water to form a ^99m Tc aqueous solution. A purification method for purifying ^99m Tc from a ⁹⁹ Mo / ^99m Tc target,
A dissolution step of dissolving the ⁹⁹ Mo / ^99m Tc target to obtain a solution;
An anion exchange column adsorption step for introducing the lysate into the anion exchange column and adsorbing ⁹⁹ Mo and ^99m Tc to the anion exchange column;
^99m Tc acquisition step of acquiring ^99m Tc adsorbed on the anion exchange column,
A method for purifying ^99m Tc, wherein the dissolution solution in the dissolution step is made alkaline. A purification method for purifying ^99m Tc from a ⁹⁹ Mo / ^99m Tc target,
Preparing an extract obtained by separating and extracting ^99m Tc with a solvent from a column on which the ⁹⁹ Mo / ^99m Tc target solution is adsorbed;
^99m Tc solution preparation step for obtaining a solution containing ^99m Tc by performing a predetermined treatment on the extract,
The predetermined treatment in the ^99m Tc solution preparation step is:
A method for purifying ^99m Tc, comprising removing the solvent from the extract by evaporating and then adding water to an aqueous solution containing ^99m Tc.

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