RU2403641C1 - METHOD OF MAKING CHROMATOGRAPHIC GENERATOR OF TECHNETIUM-99m FROM NEUTRON-IRRADIATED MOLYBDENUM-98 - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method of making a chromatographic technetium-99m generator from neutron-irradiated molybdenum-98 involves depositing a predetermined mass of molybdenum into a chromatographic column with aluminium oxide. For this purpose, eluate output of technetium-99m from the generators with different adsorbed molybdenum mass is determined. Through extrapolation from the obtained calibration curve, the mass of molybdenum which corresponds to maximum output of technetium-99m from the generator B_e=1 is found as m_i=exp[(1-a)/b], where a and b are coefficients of the calibration curve B_i=a+b·ln m_i, where B_i is the eluate output of technetium-99m from the generator for the adsorbed mass of molybdenum m_i.

EFFECT: obtaining a generator based on neutron-irradiated molybdenum-98 with a narrow eluate profile for extracting technetium-99m.

1 cl, 3 dwg

Description

The invention relates to the field of radiochemistry, in particular to methods for producing technetium-99m for medicine.

A short-lived radionuclide, technetium-99m is a daughter product of β-decay of the isotope ⁹⁹ Mo. For its rapid separation from ⁹⁹ Mo and subsequent medical use, small-sized devices — chromatographic generators of technetium [patent RU No. 2171512 C2, 07.27.2001] are most often used. They are a small chromatographic column filled with a sorbent (alumina Al ₂ O ₃ ), on which molybdenum-99 is applied. All this, together with inlet and outlet needle-communications, is placed in a protective container and transported to medical facilities, where technetium-99m is eluted from the generator with a 0.9% sodium chloride solution (saline) in the form of a ready-made preparation for intravenous administration - sodium pertechnetate, ^99m Tc.

To “charge” the generators, ⁹⁹ Mo with a high specific activity is required. In world practice, including in Russia, it is isolated from fission products of uranium-235. With this method of production, a large number of associated long-lived radioactive waste is generated, representing a high environmental hazard and requiring subsequent processing and disposal. An alternative and practically non-waste method for producing ⁹⁹ Mo is to irradiate molybdenum targets with neutrons in a reactor, reaction ⁹⁸ Mo (n, γ) ⁹⁹ Mo. With an average thermal neutron flux of 1 · 10 ¹⁴ n / cm ² · s from enriched targets, specific activity of ⁹⁹ Mo 6-8 Ci / g can be obtained, which, in principle, is sufficient for the production of chromatographic generators.

Such technology has been implemented in the USSR in the reactor INP Uz SSR in the early 90s, as well as in 2003, in Russia for IRT-T reactor Institute of Nuclear Physics at Tomsk Polytechnic University, where to increase the specific activity of ⁹⁹ Mo by reacting ⁹⁸ Mo (n, γ) ⁹⁹ Mo, reactor channels with a high content of resonance neutrons in the neutron spectrum were used [Ryabchikov AI, Skuridin VS, Nesterov EA, Chibisov EV, Golovkov VM Obtaining Molybdenum-99 in Research Reactor IR-T With Using Resonance Neutrons // Nuclear Instruments and Methods in Phys. Res., 2004, B 213, p. 344-368].

In irradiated molybdenum targets, for every ⁹⁹ Mo nuclide formed, there are approximately 10 ⁴ -10 ^-5 atoms of stable molybdenum-98 carrier. Therefore, for the manufacture of a generator from such raw materials with a nominal activity of technetium-99m 0.5 Ci (18.5 GBq) or more, about 200 mg of molybdenum must be adsorbed onto the generator column, which requires the use of oversized columns.

A method for manufacturing a generator of technetium-99m (n, γ) ⁹⁹ Mo [Miheev NB, Volkova NL, Roemer IA et al. Technetium-99m generator. // Radiochemistry, 1971, v.13, No. 4.-p.631-633], which solves the problem of applying a large amount of molybdenum to a column with Al ₂ O ₃ oxide by using saturated phosphoromolybdate solution as the sorbed form. The method allows you to sorb more than 670 mg of molybdenum (for metal) on a column with an Al ₂ O ₃ mass of more than 10 g. However, as our studies have shown and as noted in a number of works [for example, Steigman J. Chemistry of the Alumina Column / / Int. J. Apl. Radiat. Isot, 1982, V.33, p.829-834], the presence of stable molybdenum significantly affects the yield of technetium-99m from the generator. In addition, the use of large columns leads to the expansion of the elution profile of the generator. The latter means that for the complete separation of technetium-99m from the generator column, several times more saline is required than from similar generators based on the fission product of uranium-235. Accordingly, the volumetric activity of the drug is also reduced, which is also a disadvantage of the method.

A known method of manufacturing a chromatographic generator of technetium-99m from neutron-irradiated molybdenum-98 of the authors of this application, selected as a prototype [RF patent N 2276102, priority 29.11.04, bull. No. 13, 2006], which solves the problem of determining the necessary and sufficient mass of molybdenum, which provides the required activity of technetium-99m released from the generator. In accordance with this method, molybdenum is applied to alumina with a known specific activity of ⁹⁹ Mo and in such an amount that the desired technetium-99m activity is achieved by completely eluting the generator with a certain limiting volume of saline solution, a further increase of which does not increase the activity of the released radionuclide. In this case, the obtained volumetric activity of the drug is determined as the ratio of the allocated activity of technetium-99m to the total volume of saline passed through the generator column. One of the possible ways to increase the volumetric activity at a given size of the chromatographic column is to narrow its elution profile. However, this possibility is not taken into account in the prototype method, which determines its disadvantage.

Thus, the task of obtaining the highest volumetric activity of the technetium-99m preparation released from the generator with a large adsorbed mass of molybdenum remains unresolved.

The technical result of the invention consists in obtaining a generator based on molybdenum-98 neutron-irradiated with a narrow elution profile of technetium-99m emission.

The technical task is solved as follows. As in the known method, a predetermined mass of molybdenum is applied to an alumina chromatographic column. In contrast determined elyuatsionny yield of technetium-99m generators with different adsorbed mass of molybdenum, and then from the resulting calibration curve extrapolation are molybdenum mass corresponding to the maximum yield from the technetium-99m generator B = _E 1 as m _I = exp [(1- a) / c], where a and b are the coefficients of the calibration dependence B _i = a + b · lnm _i where B _i is the elution yield of technetium-99m from the generator with the adsorbed molybdenum mass m _i .

The invention is illustrated by drawings, which show:

figure 1 - change in the output of technetium-99m depending on the volume of saline passed through the columns of generators with different adsorbed mass of molybdenum: 70 mg (curve 1) and 150 mg (curve 2);

figure 2 - dependence of changes in the output of technetium-99m in _E from the logarithm of the mass of molybdenum m _Mo ;

figure 3 - elution curve of the generator with the adsorbed mass of molybdenum m _I = 0.235,

As an example, figure 1 shows the elution curves of the change in the output of technetium-99m depending on the volume of saline passed through the columns of generators with different adsorbed molybdenum mass: 70 mg (curve 1) and 150 mg (curve 2). The columns have the same volume of 7.3 cm ³ . The adsorbent used was Al ₂ O ₃ acid oxide for column chromatography (0.063-0.200 mm) from Merck, pretreated with hydrochloric acid and washed with water to pH 3. The oxide mass in the columns was 8.1 g.

From the elution curves presented, it follows that with an increase in the adsorbed molybdenum mass, the elution profile of the generator narrows. So, if in the first case, for the complete isolation of technetium-99m, the volume of saline is 20 ml, then in the second - 14 ml. This is explained as follows. As is known, the adsorption of molybdenum is carried out on the active centers of alumina. When they are incompletely filled with molybdenum, the remaining vacant centers have a “inhibitory” effect on the rate of leaching of technetium-99m from the generator, which leads to the expansion of its elution profile. In accordance with this, the problem arises of determining the required molybdenum mass, at which the narrowest profile of the generator is achieved and, as a result, the maximum yield of technetium-99m in the optimal volume of saline solution. This volume can subsequently be recommended in the operating instructions for the generator. U-235 fission product with a standard 2.8 cm column ³ - - e.g., generator produced ⁹⁹ Mo based on the recommended amount is 5 ml eluent. And for a generator made of molybdenum-98 neutron-irradiated with a column of more than 10 cm ³ , this volume can be equal to 70 ml [Molinski VJ A Review of ^99m Tc Generator Technology // Int. J. Appl. Radiat. Isot. - 1982. - v. 33. - p.811-819].

Table 1 shows the volumetric activity of the drug, calculated from the dependences of figure 1 for different volumes of saline, passed through the generator columns. The initial activity of technetium-99m in the generators was 20 GBq.

From table 1 it follows that, despite the difference in elution profiles, in both cases the highest volumetric activity of the eluate is achieved in a volume of 7-10 ml. From here, the volume of 8.5 ml can be selected as the optimum. Next, the molybdenum mass, providing the maximum yield of technetium-99m in this volume, is found from the calibration curve of the change in the yield of technetium-99m B _I from the adsorbed molybdenum mass for the limiting case B _E = 1.

The invention is illustrated by an example of a specific implementation.

A portion of 1.2 g enriched up to 98.6% molybdenum-98 with a mass of 1.2 g is irradiated in the reactor channel with a neutron flux of 1.1 · 10 ¹⁴ n / cm ² · s for 100 hours. After “cooling” the target for 10 hours, it is dissolved in 5 ml of a 5 M NaOH solution with the addition of 0.5 ml of hydrogen peroxide, and then transferred to polymolybdate with a pH of 3 by introducing 18.5 ml of a 1 M hydrochloric acid solution into the resulting solution. The specific activity of ⁹⁹ Mo in solution is 7.2 Ci / g (266.5 GBq / g), the concentration of molybdenum is C _Mo = 1.2 / 24 = 0.050 g / ml.

On pre-prepared 4 chromatographic columns with a volume of 7.3 cm ³ with 8.1 g alumina treated with hydrochloric acid and washed with water to pH 3, 2.0 is applied; 2.6; 3.0 and 3.4 ml of a solution of polymolybdate, which corresponds to the adsorbed masses of molybdenum 0.10; 0.13; 0.15 and 0.17 g. After holding the generators for 22 hours, the equilibrium accumulation of technetium-99m, they are eluted sequentially with two portions of saline solution of 8.5 and 11.5 ml in the calculation that the total release of technetium is achieved in the total volume -99m of speakers. Then measure the activity of the obtained eluates using a dose calibrator. The measurement results are presented in table 2. In its last column, the output values of technetium-99m B _i in 1 washout are calculated, calculated from the ratio of activity of 1 washout to the total activity of 1 and 2 washings. According to table 2, the dependence of the yield change of technetium-99m B _i on the logarithm of the molybdenum mass m _{i is} plotted, which is shown in FIG. 2. The dependence is described by a linear relation:

where a and b are some coefficients of the calibration dependence, which for the case under consideration are equal to 1.482 and 0.333, respectively.

By extrapolating the curve of Fig. 2 to the value of B _I = 1, we find that this limit case corresponds to lnm _Mo = -1.45. Hence, the molybdenum mass at which the maximum elution yield of technetium-99m is achieved in a given volume of saline 8.5 ml is 0.235 g. In analytical form, this result can be obtained from equation (1) by equating it to 1. According to this: ln m _I = (1-a) / c. From here:

m _I = exp [(1-a) / b] = exp [(1-1.482) / 0.333] = 0.235.

Confirmation of the claimed provisions is the elution curve of the generator with the adsorbed mass of molybdenum m _I = 0.235 g, presented in figure 3. It follows that in a volume of 8.5 ml a yield of 0.99 is achieved with a total width of the elution profile of the generator of 9 ml.

The proposed method allows to determine the adsorbed mass of molybdenum, providing a maximum yield of technetium-99m from the generator.

Table 1 m _Mo , g / v, ml Volumetric activity, GBq / ml 3 5 7 8.5 10 12 fourteen 16 eighteen twenty 0,070 0.73 1,1 1.33 1.42 1.45 1.41 1.31 1,2 1,1 1,0 0.150 1.39 1.91 2.06 2.00 1.86 1,63 1.42

table 2 Generator number m _i , g Activity ^99m Tc, GBq B _i 1 flush (8.5 ml) 2 flush (11.5 ml) one 0.10 13.3 5.2 0.72 2 0.13 19.2 4.8 0.80 3 0.15 23.5 4.2 0.85 four 0.17 27.8 2.6 0.89

Claims (1)

A method of manufacturing a technetium-99m chromatographic generator from molybdenum-98 irradiated with neutrons, comprising applying a predefined mass of molybdenum to an aluminum oxide chromatography column, characterized in that the elution yield of technetium-99m from generators with different adsorbed molybdenum mass is determined, then from the obtained calibration dependence by extrapolation find the molybdenum mass m _I corresponding to the maximum elution yield of technetium-99m from the generator B _E = 1, as m _I = exp [(1-a) / b], where a and b are the coefficients of the calibration dependence B _i = a + b · ln m _i , where B _i is the elution output of technetium-99m from the generator with the adsorbed molybdenum mass m _i .

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