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METHOD FOR MANUFACTURING AND INCREASING THE YIELD OF A MEDICAL STRONTIUM-82/RUBIDIUM-82 GENERATOR

20240194366 ยท 2024-06-13

    Inventors

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    Abstract

    Disclosed is a method for preparing a strontium-82/rubidium-82 generator. The method includes: filling a column volume with a sorbent made of hydrated tin (IV) oxide; passing through the column an initial solution with strontium-82 radionuclide, which also contains ions of stable isotopes of calcium and strontium; and washing out rubidium-82 with a saline solution of 0.9% sodium chloride. In order to achieve a breakthrough of strontium-82 or strontium-85 below permissible levels, 0.01 and 0.1 kBq per 1 MBq .sup.82Rb, respectively, when passing not less than 17 liters of saline solution through columns with a volume of not less than 1.6 cm.sup.3 and a dry sorbent weight of not less than 3.8 g, a specific activity of strontium-82 in the initial solution is not less than 90 GBq (2400 mCi) per mg of stable strontium cations for a generator with an activity of 3700 MBq (100 mCi).

    Claims

    1. A process for preparing a strontium-82/rubidium-82 generator, comprising the steps of: filling a column volume with a sorbent made of hydrated tin (IV) oxide, passing through the column an initial solution with strontium-82 radionuclide, which also contains ions of stable isotopes of calcium and strontium, washing out rubidium-82 with a saline solution of 0.9% sodium chloride, wherein to achieve a breakthrough of strontium-82 or strontium-85 below permissible levels (0.01 and 0.1 kBq per 1 MBq .sup.82Rb, respectively) when passing not less than 17 liters of saline solution through columns with a volume of not less than 1.6 cm.sup.3 and a dry sorbent weight of not less than 3.8 g, a specific activity of strontium-82 in the initial solution is not less than 90 GBq (2400 mCi) per mg of stable strontium cations for a generator with an activity of 3700 MBq (100 mCi).

    2. The process as claimed in claim 1, wherein in order to achieve a breakthrough of strontium-82 or strontium-85 not more than 0.01 kBq and 0.1 kBq per 1 MBq .sup.82Rb, respectively, when passing not less than 30 liters of saline solution through columns with a volume of not less than 1.6 cm.sup.3, and a dry sorbent weight of not less than 3.8 g, a specific activity of strontium-82 in the initial solution is not less than 180 GBq (4800 mCi) per mg of stable strontium cations for a generator with an activity of 3700 MBq (100 mCi).

    3. The process as claimed in claim 1, wherein in order to achieve a breakthrough of strontium-82 or strontium-85 not more than 0.01 kBq and 0.1 kBq per 1 MBq .sup.82Rb, respectively, when passing not less than 60 liters of saline solution through columns with a volume of not less than 1.6 cm.sup.3, and a dry sorbent weight of not less than 3.8 g, a specific activity of strontium-82 in the initial solution is not less than 290 GBq (7900 mCi) per mg of stable strontium cations for a generator with an activity of 3700 MBq (100 mCi).

    4. A process for preparing a strontium-82/rubidium-82 generator, comprising the steps of: filling a column volume with a sorbent of hydrated tin (IV) oxide, passing through the column an initial solution with strontium-82 radionuclide, which also contains ions of stable isotopes of calcium and strontium, and washing out rubidium-82 with a saline solution of 0.9% sodium chloride, wherein to achieve a breakthrough of strontium-82 or strontium-85 below permissible levels (0.01 and 0.1 kBq 1 MBq .sup.82Rb, respectively) when passing not less than 17 liters of saline solution, a content of stable isotopes of strontium and calcium in a solution containing strontium-82 radionuclide passed through the column during loading the generator is chosen such that it (1 ?mol of strontium cations+0.11 ?mol of calcium cations) does not exceed 0.67 ?mol per 1 g of dry sorbent in columns with a volume of 1.6 cm.sup.3 to 3.0 cm.sup.3 and a dry sorbent weight of 3.8 g to 7.2 g of dry sorbent.

    5. The process as claimed in claim 4, wherein in order to achieve a breakthrough of strontium-82 or strontium-85 below permissible levels (0.01 and 0.1 kBq per 1 MBq .sup.82Rb, respectively) when passing not less than 30 liters of saline solution, a content of ions of stable isotopes of strontium and calcium in the solution passed through the column during loading the generator, containing strontium-82 radionuclide, is chosen such that it (1 ?mol of strontium ions+0.11 ?mol of calcium cations) does not exceed 0.33 ?mol per 1 g of dry sorbent.

    6. The process as claimed in claim 4, wherein to achieve a breakthrough of strontium-82 or strontium-85 below permissible levels (0.01 and 0.1 kBq per 1 MBq .sup.82Rb, respectively) when passing not less than 60 liters of saline solution, a content of ions of stable isotopes of strontium and calcium in the solution passed through the column during loading the generator, containing strontium-82 radionuclide, is chosen such that it (1 ?mol of strontium ions+0.11 ?mol of calcium cations) does not exceed 0.22 ?mol per 1 g of dry sorbent.

    Description

    BRIEF DESCRIPTION OF THE DRAWINGS

    [0020] FIG. 1 shows the dependence of the total volume of eluate from the strontium-82/rubidium-82 generator before the strontium-82 breakthrough, where: 1dependence on the Sr.sup.2+ content in the generator column per 1 g of dry sorbent C.sub.Sr (Ca.sup.2+ content (C.sub.Ca=3.0 ?mol/g in all columns); 2dependence on C.sub.Ca (C.sub.Sr=0.3 ?mol/g in all columns). The volume of the columns is 1.6 cm.sup.3, the weight of the dry sorbent is 3.8 g.

    [0021] FIG. 2 shows the dependence of the ratio of .sup.82Sr activity to .sup.82Rb activity in the eluate from strontium-82/rubidium-82 generators with different volume of the generator column and the weight of the dry sorbent on the volume of the passed solution: 1the volume of the generator column is 0.34 cm.sup.3 (weight 0.8 g; C.sub.Ca=14.3 ?mol/g; C.sub.Sr=1.4 ?mol/g); 2the volume of the generator column is 1.6 cm.sup.3 (weight 3.8 g; C.sub.Ca=3.0 ?mol/g; C.sub.Sr=0.3 ?mol/g); 3the volume of the generator column 3.0 cm.sup.3 (weight 7.2 g; C.sub.Ca=1.6 mmol/g; C.sub.Sr=0.16 ?mol/g); 4the volume of the generator column 5.0 cm.sup.3 (weight 12 g; C.sub.Ca=1.0 ?mol/g; C.sub.Sr=0.1 ?mol/g). Internal diameter and height of the generator column: 1-0.4 cm and 2.7 cm; 2-0.85 cm and 2.7 cm; 3-0.85 cm and 5.4 cm; 4-1.2 cm and 4.8 cm.

    [0022] FIG. 3 shows the dependence of the total volume of eluate from the strontium-82/rubidium-82 generator before reaching the expiration limit (Expiration Limit) on the weight of the sorbent in the generator column: 1the volume of 0.34 cm.sup.3 (weight 0.8 g; C.sub.Ca=14.3 ?mol/g; C.sub.Sr=1.4 mmol/g); 2the volume of 1.6 cm.sup.3 (weight 3.8 g; C.sub.Ca=3.0 ?mol/g; C.sub.Sr=0.3 ?mol/g); 3the volume of 3.0 cm.sup.3 (weight 7.2 g; C.sub.Ca=1.6 ?mol/g; C.sub.Sr=0.16 ?mol/g); 4volume 5.0 cm.sup.3 (weight 12 g; C.sub.Ca=1.0 ?mol/g; C.sub.Sr=0.1 ?mol/g). The amount of Sr.sup.2+ in each column is 1.1 ?mol; the amount of Ca.sup.2+ in each column is 11 ?mol. Internal diameter and height of the columns: 1-0.4 cm and 2.7 cm; 2-085 cm and 2.7 cm; 3-0.85 cm and 5.4 cm; 4-1.15 cm and 4.8 cm.

    [0023] FIG. 4 shows the dependence of the total volume of eluate from the strontium-82/rubidium-82 generator before reaching the expiration limit (Expiration Limit) of strontium-82 on the volume of the generator column: 1the volume of 0.34 cm.sup.3 (weight 0.8 g; C.sub.Ca=14.3 ?mol/g; C.sub.Sr=1.4 mmol/g); 2the volume of 1.6 cm.sup.3 (weight 3.8 g; C.sub.Ca=3.0 ?mol/g; C.sub.Sr=0.3 ?mol/g); 3the volume of 3.0 cm.sup.3 (weight 7.2 g; C.sub.Ca=1.6 ?mol/g; C.sub.Sr=0.16 ?mol/g); 4volume 5.0 cm.sup.3 (weight 12 g; C.sub.Ca=1.0 ?mol/g; C.sub.Sr=0.1 ?mol/g). Internal diameter and height of the columns: 1-0.4 cm and 2.7 cm; 2-085 cm and 2.7 cm; 3-0.85 cm and 5.4 cm; 4-1.15 cm and 4.8 cm.

    [0024] FIG. 5 shows the dependence of the total volume of eluate before reaching the expiration limit (Expiration Limit) on the total content of inactive strontium and calcium cations on the sorbent in the generator column in the ratio of 0.11 C.sub.Ca+C.sub.Sr (?mol/g of the sorbent) for a standard column with a volume of 1.6 cm.sup.3 with a dry sorbent weight of 3.8 g.

    [0025] The effect of the content of inactive calcium and strontium cations on the breakthrough is different. The result of the effect of the content of inactive strontium cations on the volume of the eluate before the strontium-82 breakthrough at a constant calcium content in the sorbent is shown in FIG. 1 (line 1). The result of the effect of the content of inactive calcium cations on the volume of the eluate before the strontium-82 breakthrough at a constant strontium content in the sorbent is shown in FIG. 1 (line 2). The ratio of the effectiveness of the effect of calcium and strontium is demonstrated in Example 1 and is 0.11.

    [0026] In Example 2, Table. 2 and FIG. 2 the effect of inactive impurities on the volume of eluate is demonstrated. Both the volume of eluate before reaching the Expiration Limit and the volume of eluate before reaching the Alert Limit are given. According to the existing regulations, when the Alert Limit is achieved, control over the content of strontium isotopes in the eluate is strengthened.

    DETAILED DESCRIPTION OF THE EMBODIMENTS

    [0027] Methods for preparing a rubidium-82 generator with the claimed characteristics are confirmed by the following examples.

    Example 1

    [0028] The preparation of strontium-82/rubidium-82 generators with generator columns of the same volume is carried out in accordance with the procedure in [Zhuikov B. L., Chudakov V. M., Kohanyuk V. M. Rubidium-82 generator and method of its preparation. RU 2 546 732 CU, priority date23 Dec. 2013]. The prepared columns are: 1) with different content of calcium cations C.sub.Ca and the same content of strontium cations C.sub.Sr on the sorbent; 2) with different content of strontium cations C.sub.Sr and the same content of calcium cations C.sub.Ca on the sorbent.

    [0029] The content of strontium-82 in the eluate is measured depending on the volume of the passed eluent before the breakthrough of the strontium isotopes (V). The results are shown in Table 1 and FIG. 1.

    [0030] Table 1. Effect of the content of calcium cations C.sub.Ca or strontium cations C.sub.Sr on the sorbent in the generator column on the total volume of the obtained eluate before the strontium-82 breakthrough (V)

    TABLE-US-00001 C.sub.Ca, C.sub.Sr, ?mol/g ?mol/g V, I 3.0 0.30 16 5.9 0.30 13 8.5 0.30 10 11.1 0.30 7 3.0 0.30 16 3.0 0.66 13 3.0 0.90 10 3.0 1.50 4

    [0031] The example illustrates the different effects of strontium and calcium cations on the total eluate volume before the strontium-82 isotope breakthrough.

    [0032] The total volume of eluate before the strontium-82 breakthrough decreases with an increase of the content of both calcium cations and strontium cations on the sorbent in the generator column. In both cases, the volume of eluate before the breakthrough of strontium-82 depends linearly on concentrations C.sub.Ca and C.sub.Sr according the equation V=a.Math.C+b (where C is the concentration of calcium or strontium on the sorbent), and by the least squares method the values of parameters a and b can be determined. For calcium: a=?1.11 I.Math.g/?mol, b=19.3 I (r.sup.2=0.9996); and for strontium a=?10.14 I.Math.g/mol, b=19.3 I (r.sup.2=0.9984). Extrapolation of the linear dependence gives approximately 19 liters corresponding to a breakthrough at the strontium concentration on the sorbent C.sub.Sr=0.3 ?mol/g without calcium, or at C.sub.Sr=3.0 ?mol/g without strontium. The effect of changes in the concentration of calcium on the volume before the breakthrough is 0.11 in mol units versus the effect of changes in the concentration of strontium. Based on this, the volume before the breakthrough (V) depends on the value of 0.11.Math.C.sub.Ca+C.sub.Sr (?mol/g).

    Example 2

    [0033] The preparation of strontium-82/rubidium-82 generators with generator columns of different volumes with different sorbent weights is carried out as described in Example 1. The content of the strontium-82 isotope in the eluate is measured versus the volume of the eluent. The results are shown in Table. 2 and are illustrated also in FIG. 2. The values of C.sub.Ca and C.sub.Sr and their total amount on the sorbent are given in the description to FIGS. 3 and 4.

    [0034] Table. 2, FIGS. 3 and 4 illustrate the dependence between the total volume of eluate from the strontium-82/rubidium-82 generator before the strontium radionuclides breakthrough and the weight of the sorbent in the generator column and the volume of the generator column (hermetically sealed cylindrical container tube). This example shows that the total volume of eluate from the generator increases linearly with the weight of the sorbent or the generator column volume.

    [0035] Table 2. The volume of the passed isotonic solution of 0.9% NaCl (V) before the content of the Alert Limit (0.002 kBq.sup.82Sr/MBq .sup.82Rb) and the Expiration Limit (0.01 kBq.sup.82Sr/MBq .sup.82Rb) of the strontium-82 breakthrough in the eluate from the strontium-82/rubidium-82 generators with different volume of generator columns and the weight of the sorbent in them is reached.

    TABLE-US-00002 The volume of the passed Volume Dry Content of inactive isotonic solution before the of sorbent cations on the strontium 82 breakthrough, I column, weight, sorbent, ?mol/g Up to the Up to the cm.sup.3 g C.sub.Ca C.sub.Sr Alert Limit Expiration Limit 0.34 0.8 14.3 1.43 2 3 1.6 3.8 30 0.30 14 16 3.0 7.2 1.6 0.16 32 35 5.0 12.0 1.0 0.10 57 60
    Thus, this technical solution makes it possible to obtain an radiopharmaceutical solution with a volume of more than 30 liters by controlling the content of the main inactive impurities of strontium and calcium cations in the strontium-82 chloride solution used when loading the generator. This significantly increases the yield of the generator and reduces the risk of strontium isotope breakthrough during long-term operation of the generator (with large volumes of radiopharmaceutical solution), i.e. reduces the risk of radioactive strontium entering the patient's body.