RU2276102C1 - METHOD OF MANUFACTURE OF THE CHROMATOGRAPHIC GENERATOR OF TECHNETIUM-99m FROM IRRADIATED BY NEUTRONS MOLYBDENUM-98 - Google Patents

Abstract

FIELD: radio-chemistry; methods of production of the chromatographic generator of technetium-99m from the irradiated by neutrons molybdenum-98.

SUBSTANCE: the invention is pertaining to the field of the radio-chemistry, in particular, to the methods of production of technetium-99m for medicine. Determine the specific activity of the molybdenum and the sorptive capacity of the used aluminum oxide in molybdate-ions. The mass of the molybdenum necessary for production of the preset activity of the eluate of technetium-99m determine from the ratio: A_Tc= 0.867·L·m ln (m)/ln(m_ox·W_i), where: A_Tc - activity of the eluate of technetium-99m, Ki; L - the specific activity of molybdenum, Ki/g; m - mass of molybdenum, g; m_ox - the mass of aluminum oxide in the chromatograph column, g; W_i - the sorptive capacity of the used aluminum oxide in molybdate-ions, g/g. After making of corresponding calculations the solution of molybdenum is applied on the aluminum oxide. The technical result of the invention consists in production of the generator with the required activity of technetium-99m at usage of the minimum quantity of molybdenic raw.

EFFECT: the invention ensures production of the generator with the required activity of technetium-99m at usage of the minimum quantity of molybdenic raw.

1 ex, 2 tbl, 1 dwg

Description

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

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

To “charge” the generators, ⁹⁹ Mo with 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 of producing ⁹⁹ Mo is to irradiate neutrons in a reactor with molybdenum targets of natural composition or enriched in molybdenum-98, reaction ⁹⁸ Mo (n, γ) ⁹⁹ Mo. With an average thermal neutron flux of 1 · 10 ¹⁴ n / cm ² · s from enriched targets, a specific activity of ⁹⁹ Mo equal to 6-8 Ci / g can be obtained, which, in principle, is sufficient for the production of chromatographic generators.

A similar technology was implemented in the USSR at the INP AN Uz SSR reactor in the early 90s, and also in 2003 in Russia at the IRT-T reactor at the Research Institute of Nuclear Physics at Tomsk Polytechnic University (Skuridin BC, Chibisov EV, Nesterov EA Production of sorption generators of technetium-99m from enriched molybdenum-98 // Nuclear and Radiation Physics: Materials of the 4th International Conference, September 15-17, 2004, Almaty: INP NNC, 2004, v. 3, p. 271-275).

In irradiated molybdenum targets, for every ⁹⁹ Mo nuclide formed there are about 10 ⁴ -10 ^-5 atoms of the stable molybdenum-98 carrier. Therefore, in order to produce a generator with a nominal activity of technetium-99m of 0.5 Ci (18.5 GBq) or more from such raw materials, it is necessary to adsorb about 1 Ci ⁹⁹ Mo with a total mass of stable molybdenum exceeding 200 mg.

A known method of manufacturing a technetium-99m generator from molybdenum-98 irradiated by neutrons by the reaction (n, γ) ⁹⁹ Mo (Mikheev NB, Volkova NL, Rumer IA, etc. Generator technetium-99m // Radiochemistry , 1971, t.13, No. 4. - S.631-633), selected as a prototype, which solves the problem of applying a large amount of molybdenum to a column of aluminum oxide by using as a sorbed form a solution of saturated phosphoromolybdate and then creating a column of two layers of Al ₂ O ₃ oxide: sorption, on which molybdenum is applied, and protective - d To prevent its "slip". The method allows you to sorb more than 0.67 g of molybdenum (metal) on a column with a mass of oxide of Al ₂ O ₃ 10 g. However, as shown by our studies and as noted in a number of works (Steigman J. Chemistry of the Alumina Column // Int. J. Appt. Radiat. Isof., 1982, V.33, p.829-834), the presence of stable molybdenum significantly reduces the yield of technetium-99m from the generator. As a result, with an increase in the mass of molybdenum-98 in order to increase the total activity of ⁹⁹ Mo on the generator column, there is no proportional increase in the activity of the released ^99m Tc. The consequence of this is the unproductive consumption of expensive enriched molybdenum-98 (about 2 USD per 1 mg) and a decrease in consumer characteristics of the generator due to an increase in the width of the elution profile of technetium-99m. The prototype method of this factor does not take into account, which determines its disadvantage.

Thus, the task of determining the necessary and sufficient mass of molybdenum at its predetermined specific activity, which ensures the required activity of technetium-99m released from the generator, remains unresolved.

The technical result from the alleged invention is to obtain a generator with the required activity of technetium-99m using a minimum amount of molybdenum raw materials.

The technical task is solved as follows. As in the known method for manufacturing a technetium-99m chromatographic generator from molybdenum-98 irradiated with neutrons, a molybdenum solution is applied to alumina. In contrast, the specific activity of molybdenum and the sorption capacity of the used aluminum oxide by molybdate ions are preliminarily determined, and the required mass of molybdenum to obtain a given activity of technetium-99m eluate is found from the ratio:

And _Tc = 0.867L L m ln (m) / ln (m _OX W _I ),

where A _Tc is the activity of the technetium-99m eluate, Ki;

L is the specific activity of molybdenum, Ci / g;

m is the mass of molybdenum, g;

m _OX is the mass of alumina in the chromatographic column, g;

W _I - sorption capacity of the used alumina for molybdate ions, g / g.

As you know, the accumulation of technetium-99m in the generator occurs with a frequency of 22 hours. At the moment of complete accumulation between the activities of ^99m Tc and ⁹⁹ Mo, the equilibrium A _Tc = 0.867 A _Mo is satisfied.

In the general case, the activity of technetium-99m released from the generator at the time of its complete accumulation can be found from the relation:

where B _T is the total exit of technetium-99m from the generator when it is eluted with a certain amount of saline, a further increase of which does not increase the activity of the released radionuclide.

Experimental studies conducted on more than 150 generators showed that the relationship between the value of B _T and the adsorbed mass of molybdenum is described by the expression:

where k is a certain adsorption coefficient depending on the mass of aluminum oxide in the column of the generator m _OX and its sorption capacity W _I for molybdate ions MoO ₄ ^2- :

The physical meaning of the sorption coefficient k is as follows. As you know, the adsorption of molybdate or polymolybdate ions is carried out on the active centers of aluminum oxide, the total number N of which for these conditions for the preparation of oxide can be estimated by the ratio:

N = m _OX · N ₀ ,

where N ₀ is the density of active centers in alumina.

Accordingly, the amount of N _Mo adsorbed on molybdenum oxide will be determined by the expression:

where n is the degree of polymerization of molybdenum in the structure of the adsorbed polyanion.

It is well known that the degree of polymerization of molybdenum atoms depends on the pH of the molybdate solution. So, when changing the pH from 7 to 3 and lower, the degree of polymerization of molybdenum n increases from 1 (molybdate ions) with the subsequent formation of polyanions containing up to 7 (paramolybdate) and more molybdenum atoms. As a result, the values of sorption capacities W _i for molybdate ions and polyanions for the same pH-form of the oxide should differ n-times. In this case, in the case of adsorption of normal molybdate ions (pH ~ 7), the number of adsorbed molybdenum atoms N _Mo should most closely correspond to the number of active sites in the Al ₂ O ₃ oxide. Under these conditions the formation of ^99m Tc atom of the ⁹⁹ Mo adsorbed provided its unhindered access to the eluting solution. Similarly, during the adsorption of a polyanion with n molybdenum atoms, the greatest probability for unhindered exit of technetium-99m from its structure appears when there are n or more free (vacant) active centers around the polyanion to rearrange the remaining molybdenum atoms. Thus, the coefficient k characterizes the state of the system under which the condition N _Mo ≤N or, equivalently, m≤m _OX · W _I , which provides 100% technetium-99m output from the generator, is fulfilled.

As an example, the drawing shows the experimental dependence of the change in the yield of technetium-99m on the mass of adsorbed molybdenum obtained for generators made on the basis of chromatographic alumina (TU 6-09-3916-75). The mass of Al ₂ O ₃ oxide in the columns was 6.89 g. Molybdenum adsorption was carried out from a polymolybdate solution with pH = 3. Oxide Al ₂ O ₃ after acidification with hydrochloric acid was washed with water also to pH = 3. For the case under consideration, the coefficient k = 0.335. Accordingly, the output of technetium B _T = 1 (100%) according to relation (2) is achieved with an adsorbed molybdenum mass m = 0.048 g.

Table 1 shows the experimentally obtained values of the coefficient k for oxides of Al ₂ O ₃ with different structures, as well as different values of their masses and sorption capacities for molybdenum adsorbed from a solution with pH = 7.

Table 1. Type of oxide Al ₂ O ₃ m _OX , g W _I , g / g ln (m _{OXW I} ) k TU 6-09-3916-75 6.89 0.007 -3,032 0.335 2.81 0.007 -3.93 0.255 A-61 1,02 0,033 -3.39 0.292 A-64 1,04 0.010 -4.56 0.213 A-65 0.90 0.011 -4.61 0.215

Oxides A-61, A-64, and A-65 were obtained by electrosynthesis (Korobochkin V.V., Nesterov E.A., Skuridin BC et al. Investigation of Mo adsorption on γ-Al ₂ O ₃ with different structures // Radiochemistry, 2004, T. 46, No. 2. S.144-147).

Given the above data and relation (2), expression (1) for finding the activity of technetium-99m extracted from the generator, depending on the mass of adsorbed molybdenum, will take the form:

The invention is illustrated by examples of specific performance.

Example 1. A sample of 1.1 g enriched up to 98.6% molybdenum-98 with a mass of 1.1 g is irradiated in the reactor channel with a neutron flux of 1.1 · 10 ¹⁴ n / cm ² · s for 160 hours. After “cooling” the target for 10 h, 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 pH = 3 by adding 18.5 ml of a 1 M hydrochloric acid solution to the resulting solution. From the resulting solution with a molybdenum concentration of C _Mo = 1.1 / 24 = 0.046 g / ml, a sample of 5 μl was taken, diluted 100 times and the volumetric activity of ⁹⁹ Mo L was determined, which is 8.2 Ci / g. The same sample without dilution is introduced as a label into a pre-prepared tube containing 4-5 ml of an inactive sodium molybdate solution with pH = 7 and a total molybdenum content of 0.1 g. After mixing the mixture, a sample of 5 μl is also taken from it and the initial activity is measured A ₀ corresponding to 0.1 g of molybdenum.

A sample of Al ₂ O ₃ oxide in an amount of М≅1.0 g from the same oxide batch with which the chromatographic columns of the generators are filled is placed in a 50-ml beaker. The bulk density of Al ₂ O ₃ oxide in the columns is on average 6.89 g. The contents of the tube are introduced into the glass and mixed for 3-5 minutes. After adsorption and complete sedimentation of the mixture, a sample of 5 μl is taken from the solution layer over the oxide and its activity A _{C is} measured, which corresponds to the amount of molybdenum remaining after sorption (0.1-M · W _I ), g. The sorption capacity W _{I is} calculated from equation:

In the considered example, the value of W _I was 0.0073 g. Taking into account (2), the sorption coefficient k = -1 / ln (0.0073 · 6.89) = 0.334. When substituting the above values of L and k in equation (3) find:

Suppose that the activity of technetium-99m released from the generator should be equal to 0.5 Ci. Then from (4) determine the value of the product -m ln (m) = 0.211. To find the required mass of molybdenum m adsorbed onto the column, it is convenient to use the data in Table 2 below.

Table 2. m, g 0.04 0.05 0,07 0.09 0.11 0.125 0.150 0.175 0,200 0.250 0,300 0.400 -m ln (m) 0.128 0.150 0.186 0.217 0.243 0.260 0.285 0,305 0.322 0.347 0.361 0.366

From table 2 find that on the column of the generator should be applied 0.09 g of molybdenum. Since the concentration of molybdenum in the initial polymolybdate solution is 0.046 g / ml, 2 ml of the solution is introduced into the generator column. Subsequently, it is washed with water and saline and left for several hours to accumulate technetium-99m. Measurements of the activity of the ^99m Tc eluate obtained by pumping through a generator 9 ml of a 0.9% NaCl solution 4 hours after washing showed that A _Tc = 0.193 Ci. Subject to a correction of 0.377 by the time of complete accumulation (22 h), the activity of technetium-99m at the time of manufacture was 0.511 Ci.

Example 2. The initial data are the same as in example 1, with the difference that the activity of technetium-99m released from the generator should be equal to 0.3 Ci. From expression (4), the value −m ln (m) = 0.127 is found and the mass of adsorbed molybdenum m = 0.040 g is determined from table 2. The corresponding volume of polymolybdate is 1 ml. After washing and holding the generator for 4 hours, the activity of separated technetium-99m in the eluate with a volume of 9 ml was 0.120 Ci, and at the time of manufacture, 0.320 Ci.

The proposed method allows to reduce the consumption of molybdenum-98, as well as to optimize the sorbents according to their weight, sorption characteristics and preparation conditions.

Claims (1)

A method of manufacturing a technetium-99m chromatographic generator from molybdenum-98 irradiated with neutrons, comprising applying a molybdenum solution to alumina, characterized in that the specific activity of molybdenum and the sorption capacity of the alumina used are determined by molybdate ions, and the molybdenum mass required to obtain a predetermined activity of the technetium-99m eluate, is found from the ratio: A _Tc = 0.867L L m ln (m) / ln (m _ox W _I ), where A _Tc is the activity of the technetium-99m eluate, Ki; L is the specific activity of molybdenum, Ci / g; m is the mass of molybdenum, g; m _oh - the mass of aluminum oxide in the chromatographic column, g; W _I - sorption capacity of the used alumina for molybdate ions, g / g.