Method and apparatus for the production of high purity radionuclides

Abstract

A process for producing a daughter radionuclide from a parent radionuclide includes a) loading the parent radionuclide on a first solid medium contained in a generator and onto which the parent radionuclide is retained and whereby the daughter radionuclide is formed by radioactive decay of the parent radionuclide; b) eluting this medium with a A0 solution so as to recover a A1 solution comprising the daughter radionuclide; c) optionally adjusting the pH of the A1 solution so as to obtain a A1 solution, d) loading this A1 or A1 solution onto the head of a second solid medium contained in a chromatography column; e) first washing said second solid medium with a A2 solution; f) second washing said second solid medium with a A2 solution; g) eluting the daughter radionuclide with a A3 solution. The first washing step is conducted from head to tail of the column and the second washing step and the second eluting step are conducted from tail to head of the column.

Claims

1. A process for producing a daughter radionuclide from a parent radionuclide comprising the steps of: loading the parent radionuclide on a first solid medium contained in a generator and onto which the parent radionuclide is retained and whereby the daughter radionuclide is formed by radioactive decay of the parent radionuclide; eluting the first solid medium with a A0 solution so as to recover a A1 solution comprising the daughter radionuclide; loading the A1 solution or a A1 solution onto a head of a second solid medium contained in a chromatography column, the A1 solution being formed by adjusting a pH of the A1 solution; first washing the second solid medium with a A2 solution; second washing the second solid medium with a A2 solution; eluting the daughter radionuclide with a A3 solution, wherein in the chromatography column the first washing step is conducted from head to tail of the column and the second washing step and the second eluting step are conducted from tail to head of the column.

2. The process according to claim 1 wherein the daughter radionuclide is lead 212.

3. The process according to claim 1 wherein the parent radionuclide is chosen from radium 224, thorium 228 and their mixtures.

4. The process according to claim 1 wherein the parent radionuclide is radium 224.

5. The process according to claim 1 further comprising air-flushing the second solid medium.

6. The process according to claim 1 wherein the A2 and A2 solutions, identical or different are chosen among solutions having an acidity corresponding to that of an aqueous solution of a strong acid of concentration ranging from 0.1 to 0.5 mole/L.

7. The process according to claim 6 wherein the A2 and A2 solutions, identical or different are chosen among solutions having an acidity corresponding to that of an aqueous solution of a strong acid of concentration equal to 0.5 mole/L.

8. The process according to claim 1 wherein the A2 and A2 solutions are chosen from HCl or nitric acid solutions.

9. The process according to claim 1 wherein the A3 solution is a solution having a pH ranging from 5 to 9.

10. The process according to claim 9 wherein the A3 solution is an ammonium acetate solution.

11. The process according to claim 1 further comprising the following steps: loading radium 224 on a cation exchange resin contained in a generator; eluting with a 2 N hydrochloric acid solution so as to recover a A1 solution comprising lead 212; loading the A1 solution on the stationary phase of a liquid chromatography column; washing the column from head to tail with a A2 solution of 0.1 N hydrochloric acid; washing from the tail to head of the column with the same A2 solution; eluting from the tail to the head of the column with a A3 solution of 0.4 N ammonium acetate; and air flushing.

12. The process according to claim 1 further comprising a preliminary step of generating the parent radionuclide from a source radionuclide in a generator from which the parent radionuclide is eluted.

13. The process according to claim 2, wherein the source radionuclide is thorium 228, the parent radionuclide is radium 224 and the daughter radionuclide is lead 212.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 represents the radioactive decay chain of thorium 232.

(2) FIGS. 2-6 are diagrammatic representations of an embodiment of an apparatus for implementing the method according to the invention, in different configurations.

(3) FIGS. 7-11 are diagrammatic representations of another embodiment of an apparatus for implementing the method according to the invention, in different configurations.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

(4) The apparatus 20 of FIGS. 2-6 is configured for the automated production of a daughter radionuclide from a parent radionuclide using a generator 22 comprising the first solid medium onto which the parent radionuclide is fixed and whereby the daughter radionuclide is formed by radioactive decay of the parent radionuclide.

(5) In a known manner, the generator 22 comprises a container containing a first solid medium previously loaded with the parent radionuclide, the container allowing circulation of a solution through the container in contact with the solid medium. The generator 22 has ports for fluid connection of the container to a fluid circuit.

(6) In one embodiment, the first solid medium is loaded with radium 224 for the production of lead 212 by radioactive decay of this radium. The radium preferably has a radiological purity greater than or equal to 99.5%.

(7) The apparatus 20 comprises a fluid circuit 24 comprising a chromatography column 26, generator connection ports 28A, 28B for connecting the generator 22 to the fluid circuit 24, solution inlet ports 30A, 30B, 30C, 30D for connecting solution sources S0, S2, S3, S4 to the fluid circuit 24, and automatically actuated valves 32, 34, 36, 38, 40, 42 controlled by an electronic control unit 44.

(8) The fluid lines are illustrated in continuous lines and the control lines connecting the control unit 44 to the components of the fluid circuit 24 are illustrated as dashed lines.

(9) The fluid circuit 24 comprises two connection ports 28A, 28B, including an inlet connection port 28A for connection to an inlet of the generator 22 and an outlet connection port 28B for connection to an outlet of the generator 22.

(10) The apparatus 20 also comprises a product outlet port 46 for receiving a solution containing the daughter radionuclide and a waste outlet port 48 for receiving waste by-products.

(11) The apparatus comprises fluid lines fluidly connecting the chromatography column 26, the connection ports 28A, 28B, the inlet ports 30A, 30B, 30C, 30D, the valves 32, 34, 36, 38, 40, 42, and the outlet ports 46, 48.

(12) The chromatography column 26 is provided for purifying, by a liquid chromatography, the daughter radionuclide extracted from the generator 22, from the radiological and chemical impurities which are extracted from this generator jointly with the daughter radionuclide.

(13) This chromatography column 26 can be either a column that has been previously prepared, conditioned and calibrated, or a commercially available ready-to-use column.

(14) In all cases, the chromatography column 26 contains the second solid medium, such as an extraction chromatography stationary phase, which is capable of retaining the daughter radionuclide under certain conditions and also capable of releasing the daughter radionuclide by elution under other conditions.

(15) The chromatography column 26 comprises a head port 26A and a tail port 26B to connect the chromatography column 26 to the fluid circuit 24 of the apparatus 20.

(16) In a preferred embodiment suited to the use of the apparatus 20 in a nuclear medicine department, the sources S0, S2, S3, S4 are syringes or bags filled with a predetermined amount of appropriate fluids which are to be used during the operation of the apparatus 20. Preferably each source is suited to use in nuclear medicine: it has no rubber or silicon grease.

(17) Preferably, all the material in contact with the fluids are compatible with the acids used.

(18) In embodiment illustrated on FIG. 2, a first source S0 contains the A0 solution, a second source S2 contains the A2 solution also used as the A2 solution, a third source S3 contains the A3 solution and a fourth source S4 contains filtered air.

(19) The fluid circuit 24 comprises at least one electronically controlled pump arranged for circulating the fluids from the inlet ports 30A, 30B, 30C, 30D and through the fluid circuit 24 in the various configurations. Each pump is controlled by the control unit 44.

(20) The fluid circuit 24 of the apparatus 20 of FIG. 2 comprises a first pump 50 and a second pump 52.

(21) The fluid circuit 24 is configurable for selectively connecting the chromatography column 26, the connection ports 28A, 28B, the inlet ports 30A, 30B, 30C, 30D, the outlet ports 46, 48 and the pumps 50, 52 according to various configurations.

(22) More specifically, the valves 32, 34, 36, 38, 40, 42 are arranged and controlled for selectively connecting the chromatography column 26, the connection ports 28A, 28B and the inlet ports 30A, 30B, 30C, 30D, the outlet ports 46, 48 and the pumps 50, 52 according to different configurations.

(23) The fluid circuit 24 comprises a source selection valve 32 fluidly connected to the inlet ports 30A, 30B, 30D and to an inlet of first pump 50. The inlet ports 30A, 30B, 30D are respectively connected to the first source S0, the second source S2 and the fourth source S4. The selection valve 32 is configured for directing fluid from selectively one of the first source S0, the second source S2 and the fourth source S4 to the inlet of the first pump 50.

(24) The inlet of the second pump 52 is connected to the third source S3.

(25) The fluid circuit 24 comprises a by-pass valve 34 fluidly connected to the outlet of the first pump 50, to the second pump 52, to the inlet connection port 28A and to a distribution valve 36 of the fluid circuit 24. The by-pass valve 34 is configured for selectively directing fluid from the first pump 50 to the inlet connection port 28A, from the first pump to the distribution valve 36 or from the second pump 52 to the distribution valve 36.

(26) The distribution valve 36 is fluidly connected to the by-pass valve 34, to the outlet connection port 28B, to a head valve 38 and a tail valve 40 of the fluid circuit 24. The distribution valve 36 is configured for selectively directing fluid form the by-pass valve 34 to the head valve 38 or from the by-pass valve 34 to the tail valve 40 or from the outlet connection port 28B to the head valve 38.

(27) The head valve 38 is fluidly connected to the distribution valve 36, to a head port 26A of chromatography column 26 and to an outlet valve 42. The head valve 38 is configured for selectively receiving fluid from the distribution valve 36 and providing the fluid to the head port 26A or receiving fluid from the head port 26A and providing the fluid to the outlet valve 42 or receiving fluid from the distribution valve 36 and providing the fluid to the outlet valve 42.

(28) The tail valve 40 is connected to the distribution valve 36, to a tail port 26B of the chromatography column 26 and to the outlet valve 42. The tail valve 40 is configured for selectively receiving fluid from the distribution valve 36 and providing the fluid to the tail port 26B or receiving fluid from the tail port 26B and providing the fluid to the outlet valve 42.

(29) The outlet valve 42 is connected to the head valve 38, to the tail valve 40, to the product outlet port 46 and to the waste outlet port 48. The outlet valve 42 is configured for receiving fluid selectively from the head valve 38 or the tail valve 40 and providing the fluid selectively to the product outlet port 46 or to the waste outlet port 48.

(30) A product flask 49 is connected to the product outlet port 46. Preferably, a filter 49A is placed at the entrance to the product flask 49 to complete the chemical purification of daughter radionuclide by a bacteriological purification. The filter 49A has for example a pore size or pore diameter of 0.2 m.

(31) A waste receptacle 51 is connected to the waste outlet port 48 for collecting waste by-product solutions from the fluid circuit 24, generated during operation of the apparatus 20.

(32) The different configurations of the fluid circuit 24 are illustrated in FIGS. 2-6, in which the bold fluid lines are the fluid lines in which the fluid circulates and the thin fluid lines are the fluid lines in which no fluid circulates.

(33) In a first elution configuration (FIG. 2), the fluid circuit 24 is configured for circulating the A0 solution from the inlet port 30A and through the generator 22 to recover the A1 solution containing the daughter radionuclide and for circulating the A1 solution from the generator 22 through the chromatography column 26 frontward from head to tail.

(34) In the first elution configuration, the valves 32, 34, 36, 38, 40, 42 are controlled such that the A0 solution flows from the first source S0 successively through the valve 32, through the first pump 50, through the by-pass valve 34 and through the generator 22, and the A1 solution exiting the generator 22 flows through the distribution valve 36, through the head valve 38, through the chromatography column 26 from head port 26A to tail port 26B, through the tail valve 40, through the outlet valve 42 and to the waste outlet port 48.

(35) In a frontward washing configuration (FIG. 3), the fluid circuit 24 is configured for circulating the A2 solution from the second source S2 through the chromatography column 26 from head port 26A to tail port 26B.

(36) In the frontward washing configuration, the valves 32, 34, 36, 38, 40, 42 are controlled such that the A2 solution flows from the second source S2 successively through the valve 32, through the first pump 50, through the by-pass valve 34, through the distribution valve 36, through the head valve 38, through the chromatography column 26 from head port 26A to tail port 26B, through the tail valve 40, through the outlet valve 42 and to the waste outlet port 48. In the frontward washing configuration, the generator 22 is by-passed.

(37) In a backward washing configuration (FIG. 4), the fluid circuit 24 is configured for circulating the A2 solution through the chromatography column 26 from tail port 26B to head port 26A. The A2 solution is here the same as the A2 solution and is circulated from the second source S2.

(38) In the backward washing configuration, the valves 32, 34, 36, 38, 40, 42 are controlled such that the A2 solution flows from the second source S2 successively through the valve 32, through the first pump 50, through the by-pass valve 34, through the distribution valve 36, through the tail valve 40, through the chromatography column 26 from tail port 26B to head port 26A, through the head valve 38, through the outlet valve 42 and to the waste outlet port 48. In the backward washing configuration, the generator 22 is by-passed.

(39) In a second elution configuration (FIG. 5), the fluid circuit 24 is configured for circulating the A3 solution from the third source S3 through the chromatography column 26 from tail port 26B to head port 26A.

(40) In the second elution configuration, the valves 32, 34, 36, 38, 40, 42 are controlled such that the A3 solution flows from the third source S3 successively through the second pump 52, through the by-pass valve 34, through the distribution valve 36, through the tail valve 40, through the chromatography column 26 from tail port 26B to head port 26A, through the head valve 38, through the outlet valve 42. In the second elution configuration, the generator 22 is by-passed.

(41) In the second elution configuration, the outlet valve 42 is controlled to flow the fluid selectively to the product outlet port 46 or the waste outlet port 48. Preferably, in a first phase (not shown), the outlet valve 42 is controlled to flow the fluid to the waste outlet port 48 and then, in a subsequent second phase, the outlet valve 42 is controlled to flow the fluid to the product outlet port 46 (FIG. 5). The first phase allows to discard the first elution fraction which aims at increasing the pH and does not contain or contain only few daughter radionuclide, whereas the second phase allows to collect the second elution fraction which actually elutes the daughter radionuclide and is enriched in the daughter radionuclide. In an alternative, the first phase is omitted and the outlet valve 42 is controlled to flow the fluid to the product outlet port 46 permanently during the second elution configuration.

(42) In a flushing configuration (FIG. 6), the fluid circuit 24 is configured for circulating air from the fourth source S4 to the product outlet 46 and/or to the waste product outlet 48 for flushing the fluid circuit 24 with air.

(43) In the flushing configuration, the valves 32, 34, 36, 38, 40, 42 are controlled such that the air flows from the fourth source S4 to the product outlet port 46 with passing successively through the valve 32, the pump 50, the by-pass valve 34, the distribution valve 36, the head valve 38 and the outlet valve 42.

(44) The outlet valve 42 is controlled for directing air sequentially to one of the product outlet 46 and the waste product outlet 48 and then to the other, for flushing the corresponding fluid lines. In the flushing configuration, the generator 22 and the chromatography column 26 are by-passed.

(45) As illustrated on FIGS. 2-6, the apparatus 20 comprises a sealed enclosure 54 defining a chamber 56 containing the fluid circuit 24. The inlet ports 30A, 30B, 30C, 30D, the connection ports 28A, 28B and the outlet ports 46, 48 allow to connect respectively sources S1, S2, S3, S4, the generator 22 and the product and waste receptacles 49, 51 to the fluid circuit 24 from outside the enclosure 54.

(46) FIGS. 7-11, in which same or similar parts use same references, illustrate another apparatus 20 configured for the automated production of a daughter radionuclide from a parent radionuclide using a generator 22 comprising a solid medium onto which the parent nuclide is fixed and whereby the daughter nuclide is formed by radioactive decay of the parent nuclide.

(47) The apparatus 20 of FIGS. 7-11 uses fewer valves than the apparatus of FIGS. 2-6.

(48) The fluid circuit 24 of the apparatus 20 of FIGS. 7-11 comprises an inlet valve 32 fluidly connected to the inlet ports 30A, 30B, 30C, 30D and an outlet connected to the inlet of a pump 60. The inlet valve 32 is configured for directing fluid from selectively one of the inlet ports 30A, 30B, 30C, 30D to the inlet of the pump 60.

(49) The fluid circuit 24 comprises a distribution valve 62 fluidly connected to the outlet of the pump 60 and to the inlet connection port 28A, the head valve 38 and the tail valve 40. The distribution valve 62 is configured for connecting the outlet of the pump 60 to selectively one of the inlet connection port 28A, the head valve 38 and the tail valve 40.

(50) The outlet connection port 28B is fluidly connected to the fluid line connecting the distribution valve 62 to the head valve 38. Fluid exiting the generator 22 is injected into the fluid line connecting the distribution valve 62 to the head valve 38.

(51) The head valve 38 is fluidly connected to the distribution valve 62, to a head port 26A, to the product outlet port 46 and to the waste outlet port 48. The head valve 38 is configured for selectively directing fluid from the distribution valve 62 to the head port 26A or directing fluid from the head port 26A to the outlet port 46 or directing fluid from the head port 26A to the outlet port 48.

(52) The tail valve 40 is connected to the distribution valve 62, to a tail port 26B, to the outlet port 46 and to the outlet port 48. The tail valve 40 is configured for selectively directing fluid from the distribution valve 62 to tail port 26B, directing fluid from the tail port 26B to the outlet port 46 or directing fluid from the tail port 26B to the outlet port 48.

(53) The apparatus 20 of FIGS. 7-11 allows configurations functionally similar to that of the apparatus of FIGS. 2-6, namely a first elution configuration, a frontward washing configuration, a backward washing configuration, a second elution configuration and a flushing configuration.

(54) In the first elution configuration (FIG. 7), the valves 32, 62, 38, 40 are controlled such that the A0 solution flows from the first source S0 successively through the selection valve 32, through the pump 60, through the distribution valve 62 and through the generator 22, the A1 solution exiting the generator 22 circulating through the head valve 38, through the chromatography column 26 from head port 26A to tail port 26B, through the tail valve 40 and to the waste outlet port 48.

(55) In the first washing configuration (FIG. 8), the valves 32, 62, 40, 38 are controlled such that the A2 solution flows from the second source S2 successively through the selection valve 32, through the pump 60, through the distribution valve 62, through the head valve 38, through the chromatography column 26 from head port 26A to tail port 26B, through the tail valve 40 and to the waste outlet port 48.

(56) In the second washing configuration (FIG. 9), the valves 32, 62, 40, 38 are controlled such that the A2 solution (which is here the same as the A2 solution) flows from the second source S2 successively through the selection valve 32, through the pump 60, through the distribution valve 62, through the tail valve 40, through the chromatography column 26 from tail port 26B to head port 26A, through the head valve 38 and to the waste outlet port 48 (see arrows and references A2).

(57) In the second elution configuration (FIG. 10), the valves 32, 62, 40, 38 are controlled such that the A3 solution flows from the third source S3 successively through the selection valve 32, through the pump 60, through the distribution valve 62, through the tail valve 40, through the chromatography column 26 from tail port 26B to head port 26A and through the head valve 38 (see arrows and references A3).

(58) In the second elution configuration, the head valve 38 is controlled to flow the fluid selectively to the product outlet port 46 or the waste outlet port 48. Preferably, in a first phase (not shown), the head valve 38 is controlled to flow the fluid to the waste outlet port 48 and then, in a subsequent second phase, the head valve 38 is controlled to flow the fluid to the product outlet port 46 (FIG. 10). In an alternative, the first phase is omitted and the head valve 38 is controlled to flow the fluid to the product outlet port 46 permanently during the second elution configuration.

(59) In the flushing configuration (FIG. 11), the valves 32, 62, 40, 38 are controlled such that the air flows from the fourth source S4 successively through the selection valve 32, through the pump 60, through the distribution valve 62 and through the tail valve 40. The tail valve 40 is controlled for directing air sequentially to one of the product outlet port 46 and the waste outlet port 48 and then to the other for flushing the fluid circuit 24 with air.

(60) The apparatus of FIGS. 7-11 allows reducing the number of valves and thus makes the apparatus easier and more economical to manufacture.

(61) Advantageously, the ports are provided with a color code for avoiding an operator to make any mistake upon connecting the S0, S2, S3, S4 sources, the generator 22 and the receptacles 49, 51 to the fluid circuit 24.

(62) In one embodiment, the pumps 50, 52 and 60 are syringe-pumps controllable to retrieve from a source a predetermined amount of fluid and to inject said determined amount into the fluid circuit 24.

(63) In the embodiments of FIGS. 2-6 and 7-11, the enclosure 54 prevents access to fluid circuit 24. The enclosure comprises a lockable access device such as a door to allow access to the chamber 56. This makes it possible to prevent any non-qualified persons from accessing the fluid circuit 24 of the apparatus 20, particularly the components having some radiological activity, or the components whose functioning can be damaged.

(64) In the embodiments of FIGS. 2-6 and 7-11, the generator 22 is located outside the enclosure 54 and is removably connectable to the fluid circuit 24 via the connection ports 28A, 28B. This allows replacing the generator 22 by another similar generator. Indeed, due to the lifetime of the parent radionuclide, the generator can only be used for a limited period of time. For example, the radium 224 has a half-life time of 3.66 days.

(65) In a similar manner, the chromatography column 26 can be disconnected from the fluid circuit 24 for replacement by another similar column.

(66) The general dimensions of the various components of the apparatus 20 are relatively small, which makes it possible to arrange them in an enclosure 54 which is also small in size. The apparatus 20 can therefore be a portable apparatus that can be used close to the area of usage of the daughter radionuclide, e.g. the lead 212.

(67) The apparatus 20 has several inlet ports 30A, 30B, 30C, 30D to which the different sources S0, S2, S3, S4 of fluids are connected to the apparatus 20. Preferably, each source S0, S2, S3, S4 is associated with a respective inlet port 30A, 30B, 30C, 30D.

(68) In order to avoid any reversal between the sources S0, S2, S3, S4, the apparatus 20 comprises so-called failsafe features allowing an operator to correctly connect each source S0, S2, S3, S4 to the corresponding inlet port 30A, 30B, 30C, 30D.

(69) According to an embodiment, the failsafe features are visual features, e.g. a color coding. Each source S0, S2, S3, S4 has a color code and the corresponding inlet port 30A, 30B, 30C, 30D has the same color code.

(70) Alternatively or optionally, each source S0, S2, S3, S4 and the corresponding inlet port 30A, 30B, 30C, 30D has complementary fool proofing shapes such that each source S0, S2, S3, S4 is connectable only to the corresponding inlet port 30A, 30B, 30C, 30D. In this way it becomes impossible to connect a source to an inlet port with which it is not associated, thus preventing any human error.

(71) Each apparatus of FIGS. 2-6 and 7-11 makes it possible to implement the method of the invention in an automated manner. The valves 32, 34, 36, 38, 40, 42; 32, 62, 38, 40 and the pumps 50, 52, 60 are automatically controlled by the control unit 44 for implementing the method of the invention.

(72) In operation, the daughter radionuclide is produced in the generator 22 by radioactive decay of the parent radionuclide and the daughter radionuclide is retained on the first solid medium.

(73) The control unit 44 is configured for successively operating the first elution configuration, the frontward washing configuration, the backward washing method and the second elution method, and, optionally, the purging method.

(74) Extraction of the Daughter Radionuclide (FIG. 2 or 7)

(75) The apparatus 20 is configured in the first elution configuration. The A0 solution is circulated through the generator 22 and the A1 solution containing the daughter solution exits the generator 22.

(76) Loading to the Chromatography Column (FIG. 2 or 7)

(77) The apparatus 20 still being in the first elution configuration, the A1 solution exiting the generator 22 is circulated through the chromatography column 26 from head to tail. The daughter radionuclide is retained by the second solid medium contained in the chromatography column 26.

(78) Frontward Washing of the Chromatography Column (FIG. 3 or 8)

(79) The apparatus 20 is configured in the first washing configuration. The A2 solution is circulated through the chromatography column 26 from head to tail. The A2 solution removes radiological and chemical impurities from the second solid medium while the daughter radionuclide is retained by the second solid medium.

(80) Backward Washing of the Chromatography Column (FIG. 4 or 9)

(81) The apparatus 20 is configured in the backward washing configuration. The A2 solution is circulated through the chromatography column 26 from tail to head. The A2 solution removes radiological and chemical impurities from the second solid medium while the daughter radionuclide is retained by the second solid medium.

(82) Second Elution of the Chromatography Column (FIG. 5 or 10)

(83) The apparatus 20 is configured in the second elution configuration. The A3 solution is circulated through the chromatography column 26 from tail to head. The A3 solution removes the daughter radionuclide from the second solid medium and is collected in a collecting device, e.g. in the product flask 49.

(84) Preferably, in a first phase of the second elution, the fluid flows to the waste outlet port 48 and then, in a subsequent second phase of the second elution, the fluid flows to the product outlet port 46. The first phase allows discarding the first elution fraction which aims at increasing the pH and does not contain or contain only few daughter radionuclide, whereas the second phase allows to collect the second elution fraction which actually elutes the daughter radionuclide and is enriched in the daughter radionuclide. In an alternative, the first phase is omitted and the fluid flows to the product outlet port 46.

(85) Purging of the Apparatus (FIG. 6 or 11)

(86) The apparatus 20 is configured in the flushing configuration. The purified air is circulated from the source S4 to product receptacle 49 and/or the waste receptacle 51 to flush components of the fluid circuit 24.

(87) The following examples are given as an illustration of an embodiment of the invention, for non-limiting purposes.

EXAMPLES

Example 1

(88) Lead 212 was produced with an apparatus similar to the one that has just been described and by a process comprising the following steps:

(89) A radium 224 generator containing 400 mg of a cation exchange resin (company BIO-RADreference AG MP50) as the solid medium was used. The resin was initially loaded with 30 mL of a solution containing 173 MBq of radium 224 of radiological purity greater than 99.5% (such as that determined by spectrometry).

(90) The system without the generator was loaded with 2 mL of a 2N HCl solution at the loading rate of 1 mL/min.

(91) The generator was then eluted with 5 mL of a 2N HCl solution at the elution rate of 0.5 mL/min. The resulting solution was then loaded on the head of the chromatography column.

(92) A ready-to-use chromatography column containing 8010 mg of Pb resin (company TRISKEM International) as the stationary phase was washed with 1 mL of a 0.1N HCl solution at the washing rate of 0.5 mL/min.

(93) It was then washed in a backward fashion with 1 mL of a 0.1N HCl solution at the washing rate of 0.5 mL/min.

(94) 0.5 mL of an aqueous solution containing 0.4 mol/L of ammonium acetate (pH 6.5) was used to load the system (loading rate: 0.5 mL/min).

(95) 1 mL of an aqueous solution containing 0.4 mol/L of ammonium acetate (pH 6.5) was used to elute the Pb column in a backward fashion (elution rate: 0.25 mL/min) to elute the lead 212 from the stationary phase of the chromatography column and recover it at the head of the column.

(96) The system was then flushed with sterile air (0.2 m filter) (1 mL at 1 mL/min).

(97) Radium 224 was left to generate lead 212 for 19 h and 82 MBq of lead 212 were obtained.

(98) After a second delay of 24h, the system yielded 80 MBq of lead 212. A third cycle after another 24 h lead to 64 MBq of lead 212.

(99) The lead 212 obtained exhibited a radiological purity of more than 99.95%, generally about 99.995%. The grade is such that even radium 224 was not detectable after 1 week.

(100) Its chemical purity was characterized by the presence, in the lead 212 elution solution, of: less than 25 ppb (parts per billion) of lead (other than lead 212) and manganese; less than 2 ppb of cobalt, copper, molybdenum, cadmium, thorium, tungsten and mercury; less than 2 ppm of vanadium, iron and zinc.

(101) Its bacteriological purity was characterized by sterility and less than 0.5 endotoxin unit/mL; and this in less than 20 minutes between the start of the extraction of lead 212 from the radium 224 generator and the end of the filling of the flask 46 with purified lead 212.

Example 2

(102) Lead 212 was produced with an apparatus similar to the one that has just been described and by a process comprising the following steps:

(103) A radium 224 generator containing 400 mg of a cation exchange resin (company BIO-RADreference AG MP50) as the solid medium was used. The resin was initially loaded with 24 mL of a solution containing 169 MBq of radium 224 of radiological purity greater than 99.5% (such as that determined by spectrometry).

(104) The system without the generator was loaded with 2 mL of a 2N HCl solution at the loading rate of 1 mL/min.

(105) The generator was then eluted with 5 mL of a 2N HCl solution at the elution rate of 0.5 mL/min. The resulting solution was then loaded on the head of the chromatography column.

(106) A ready-to-use chromatography column containing 8010 mg of Pb resin (company TRISKEM International) as the stationary phase was washed with 1 mL of a 0.1N HCl solution at the washing rate of 0.5 mL/min.

(107) It was then washed in a backward fashion with 1 mL of a 0.1N HCl solution at the washing rate of 0.5 mL/min.

(108) 0.5 mL of an aqueous solution containing 0.4 mol/L of ammonium acetate (pH 6.5) was used to load the system (loading rate: 0.5 mL/min).

(109) 1 mL of an aqueous solution containing 0.4 mol/L of ammonium acetate (pH 6.5) was used to elute the Pb column in a backward fashion (elution rate: 0.25 mL/min) to elute the lead 212 from the stationary phase of the chromatography column and recover it at the head of the column.

(110) The system was then flushed with sterile air (0.2 m filter) (1 mL at 1 mL/min).

(111) Radium 224 was left to generate lead 212 for 20 h and 81 MBq of lead 212 were obtained,

(112) After a second delay of 21 h, the system yielded 71 MBq of lead 212. A third cycle after another 9 h lead to 40 MBq of lead 212.

(113) The lead 212 obtained exhibited a radiological purity of more than 99.95%, generally about 99.995%. The grade is such that even radium 224 was not detectable after 1 week.

(114) Its chemical purity was characterized by the presence, in the lead 212 elution solution, of: less than 17 ppb (parts per billion) of lead (other than lead 212) and manganese; less than 2 ppb of cobalt, tungsten, thorium and mercury; less than 0.1 ppm of copper, molybdenum, iron and cadmium; less than 3 ppm of vanadium and zinc.

(115) Its bacteriological purity was characterized by sterility and less than 0.5 endotoxin unit/mL; and this in less than 20 minutes between the start of the extraction of lead 212 from the radium 224 generator and the end of the filling of the flask 46 with purified lead 212.