RADIOISOTOPE GENERATOR

Abstract

The invention relates to a radioisotope generator (1) comprising an eluent reservoir (2) and a chromatographic column (3) connected to one another by a first eluent duct (4), characterized in that it comprises a second duct (7) and a valve (8) connected said second duct (7) to the first eluent duct and the first eluent duct, said valve (8) having a first position where the second duct (7) communicates with the first eluent duct (4) and a second position where the second duct (7) communicates with the first eluent duct (4), said second duct (7) having a bypass segment (9) for a predetermined eluent volume.

Claims

1. A radioisotope generator (1), comprising an eluent reservoir (2) and a chromatographic column (3) connected to one another by a first eluent transmission duct (4), said chromatographic column (3) having a stationary phase loaded with a parent radioisotope disintegrating spontaneously into a daughter radioisotope, said generator being characterized in that it comprises a second duct (7) and a valve (8) housed between an upstream part (4′) of the first eluent duct (4) and a downstream part (4″) of the first eluent duct (4), and connecting said second duct (7) to said upstream part (4′) of the first eluent duct and to the downstream part (4″) of the first eluent duct, said valve (8) having a first position in which the second duct (7) is in fluid communication with said upstream part (4′) of the first eluent duct (4) and a second position in which the second duct (7) is in fluid communication with said downstream part (4″) of the first eluent duct (4), said second duct (7) having a bypass segment (9) for a predetermined volume of eluent, said segment (9) being defined directly between said valve (8) and a segment end (9′), said predetermined eluent volume being a sufficient volume to obtain, when said sufficient volume crosses through the chromatographic column (3), under the action of a driving force of the eluent, an eluate comprising a parent radioisotope activity comprised in a value range from 0.0% to 30.0% relative to a daughter radioisotope activity of said eluate.

2. The generator according to claim 1, wherein said reservoir (2) is situated above said chromatographic column (3), said segment (9) end (9′) being positioned at a sufficient height (H), measured from an apical end (16) of the chromatographic column (3), such that the gravitational force has a sufficient intensity to allow a flow of the eluent through the segment (9).

3. The generator according to claim 2, wherein at least one bypass segment part (9) connected to said valve (8) is inclined relative to a horizontal plane (h) by an angle α defined between said horizontal plane and a line (d) secant to said horizontal plane, said angle α having a predetermined value such that its sine value is greater than 0 and less than or equal to 1, and its cosine value is between −1 and 1.

4. The generator according to claim 1, wherein said segment end (9′) corresponds to a free end (15) of the second duct (7).

5. The generator according to claim 1, comprising means for blocking the eluent (17) in fluid communication with said bypass segment (9), so as to block the passage of said eluent volume past said segment (9) end (9′).

6. The generator according to claim 5, wherein said segment (9) end (9′) is directly connected to a first sterile filter (17) with a polarity opposite that of said eluent, said first sterile filter (17) being said blocking means of the eluent (17).

7. The generator according to claim 1, wherein said free end (15) is connected to a second sterile filter (17) with an inverse polarity relative to that of said eluent.

8. The generator according to claim 6, comprising a pumping means (MP) arranged to be connected hermetically to an eluate outlet (12) and designed to pump, once said valve (8) is in its second position and after elution of the stationary phase of the chromatographic column (3) by said sufficient volume of eluent, a fluid from the segment (9) end (9′) or from the free end (15) of the second duct (17) toward the eluate outlet, said fluid being a remaining fraction of said sufficient volume of eluent present in the column or ambient air pumped from said free end (15) or said segment (9) end (9′) of said second duct (7).

9. The generator according to claim 8, wherein said pumping means (MP) is a vacuum container.

10. The generator according to claim 8, wherein the pumping means (MP) is an actuator (18) comprising a piston (19) mounted in a cylinder (20), said cylinder having a first end (21) communicating with said eluate outlet (12) of the chromatographic column, said piston (19) being extended by an arm (22) that extends outside said cylinder through an orifice (23) present on a second cylinder end (24), opposite the first cylinder end (21), said piston having a first idle position (R) and a fluid pumping position (P), said piston (19), when it is set in motion between said first idle position (R) and said pumping position (P), generating a pumping force for the fluid.

11. The generator according to claim 1, positioned in a shielded box C, said box preferably being at least partially made from a dense material, for example tungsten or lead.

12. The generator according to claim 1, wherein the parent radioisotope activity is comprised in a value range from 0.0% to 20%, advantageously from 0.0% to 10%, more preferably from 0.0% to 5.0%, still more preferably from 0.0% to 2.0%, more advantageously from 0.0% to 1.0%, relative to the daughter radioisotope activity of said eluate.

13. The generator according to claim 12, wherein the parent radioisotope activity is equal to 0.0 mCi.

14. An elution method for a chromatographic column of a radioisotope generator (1) comprising an eluent reservoir (2) and connected to a chromatographic column (3) by a first eluent duct (4), said chromatographic column (3) having a stationary phase impregnated with eluent and loaded with a parent radioisotope disintegrating spontaneously into a daughter radioisotope, said method comprising the following steps: withdrawing a predetermined volume in a withdrawal segment (9) of a second eluent duct (7) connected to an upstream part (4′) of the first eluent duct (4) and to a downstream part (4″) of the first eluent duct (4) by a valve (8), said withdrawal segment (9) being defined directly between the valve (8) and a segment end (9′), the withdrawal being done when the valve (8) is in a first position in which the second duct is in fluid communication with said upstream part of the first eluent duct; and an elution, under the action of a driving force of the eluent, of said predetermined volume of eluent from said withdrawal segment (9) toward said chromatographic column (3) when the valve (8) is in a second position in which the second duct (7) is in fluid communication with said downstream part (4″) of the first eluent duct, a step for drying the column by pumping sterilized ambient air from the segment (9) end (9′) or from a free end (15) of the second duct (17) toward the eluent outlet (12), said predetermined eluent volume being a sufficient volume to obtain, when said sufficient volume crosses through the chromatographic column, an eluate comprising a parent radioisotope activity comprised in a value range from 0.0% to 30.0% relative to a daughter radioisotope activity of said eluate.

15. The method according to claim 14, comprising a step for blocking the eluent, after said injection step, so as to block the passage of said volume of eluent past said segment (9) end (9′).

16. The method according to claim 14, comprising a bleeding step, carried out before the drying step, when said valve (8) is in its second position and after elution of the stationary phase of the chromatographic column (3) by the sufficient eluent volume, consisting of pumping a remaining fraction of the sufficient volume of eluent present in the column toward a bleed container connected beforehand to a column (3) outlet (12).

17. The method according to claim 14, wherein the parent radioisotope activity is comprised in a value range from 0.0% to 20%, advantageously from 0.0% to 10%, more preferably from 0.0% to 5.0%, still more preferably from 0.0% to 2.0%, more advantageously from 0.0% to 1.0%, relative to the daughter radioisotope activity of said eluate.

18. The method according to claim 17, where the parent radioisotope activity is equal to 0.0 mCi.

Description

[0062] Other features and advantages of the invention will emerge from the description provided below, non-limitingly and in reference to the examples described below.

[0063] FIG. 1 diagrammatically shows a first embodiment of the generator according to the invention.

[0064] FIGS. 2a and 2b diagrammatically illustrate two possible alternatives of a second embodiment of the generator according to the invention.

[0065] FIG. 3 diagrammatically shows a third embodiment of the generator according to the invention.

[0066] In these figures, similar elements bear the same references.

[0067] The radioisotope generator 1 according to the invention shown in FIG. 1 comprises an eluent reservoir 2 and a chromatographic column 3 connected to one another by a first eluent transmission duct 4, such that the eluent contained in the reservoir 2 is in fluid communication with the chromatographic column 3.

[0068] The chromatographic column 3 comprises a stationary phase impregnated with eluent and loaded with a parent radioisotope disintegrating spontaneously into a daughter radioisotope.

[0069] The first eluent transmission duct 4 connects an eluent inlet 5 positioned upstream from the stationary phase 2 to an eluent outlet 6 of the reservoir 2.

[0070] The radioisotope generator 1 further comprises a second duct 7 and a valve 8 connecting an upstream part 4′ of the first eluent duct and a downstream part 4″ of the first eluent duct. The upstream part 4′ connects the eluent outlet 6 of the reservoir 2 to a first inlet 8′ of the valve 8, while the downstream part 4″ connects a second inlet 8″ of the valve 8 to the eluent inlet 5 of the chromatographic column 3.

[0071] The valve 8 further connects an end 7′ of the part connected to the second duct 7 to the upstream part 4′ and downstream part 4″ of the first eluent duct 4. The second duct 7 is placed in fluid communication with the valve 8 by means of a connection between the end 7′ of the connected part of the second duct 7 and a third inlet 8′″ of the valve 8.

[0072] In this context, the valve 8 has a first position in which the second duct 7 is in fluid communication with the upstream part 4′ of the first eluent duct 4 and a second position in which the second duct 7 is in fluid communication with the downstream part 4″ of the first eluent duct 4.

[0073] The second duct 7 further has a bypass segment 9 for a predetermined volume v of eluent. The segment 9 is defined directly between the valve 8 and a segment end 9′.

[0074] Typically, the predetermined volume v of eluent is defined by a bypass segment length and a bypass segment diameter.

[0075] In the first embodiment as described in FIG. 1, the segment 9 is defined between the end 7′ of the connected part of the second duct 7 and the segment end 9′.

[0076] In particular, the segment end is connected to a blocking means 17 of the eluent in fluid communication with the bypass segment 9, so as to block the passage of the eluent volume beyond the segment end 9′.

[0077] The blocking means 17 can for example be a sterile filter with a polarity opposite that of the eluent whose function is to allow ambient air to pass in the bypass segment 9 and to block the passage of the eluent in a defined direction from the end 7′ of the connected part of the second duct 7 toward the segment end 9′.

[0078] Preferably, the generator 1 is placed in a shielded box C for example at least partially made from a dense material, for example tungsten or lead. The box C comprises a first access opening 10 to the reservoir 2 and an outlet opening 11 positioned downstream from an eluate outlet 12 of the chromatographic column 3 and arranged to be crossed through by a second eluate outlet duct 12′ arranged to connect the eluate outlet 12 of the column 3 to an eluate container 13 arranged to be positioned in a chamber 14 arranged in the box and positioned downstream from the outlet opening 11. Preferably, the eluate container 13 and/or the chamber 14 comprise(s) shielding made from a dense material, for example tungsten or lead.

[0079] In the first embodiment as illustrated in FIG. 1, the reservoir 1 is positioned above the chromatographic column 3.

[0080] The end 9′ of the bypass segment 9, which can for example be a free and 15 of the second duct 7, is positioned at a predetermined height H, measured from an apical end 16 of the chromatographic column 3.

[0081] Optionally, at least one bypass segment part 9 connected to the valve 8 is inclined relative to a horizontal plane h by an angle α defined between the horizontal plane h and a line d secant to the horizontal plane h.

[0082] Advantageously, the angle α has a predetermined value such that its sine value is greater than 0 and less than or equal to 1 and its cosine value is comprised between −1 and 1.

[0083] During the operation of the first embodiment of the generator (FIG. 1), the valve 8 is first positioned in its first position. The eluent flows from the reservoir 2 through the upstream part 4′ of the first duct 4 toward the second duct 7.

[0084] The bypass segment 9 fills, under the effect of the gravitational force that acts on a volume V of eluent contained in the reservoir 2, by the predetermined volume v of eluent according to a bypass flow rate at a value predetermined by the length of the bypass segment diameter 9.

[0085] The air contained in the segment is driven toward the sterile filter 17 by the eluent. The travel of the eluent from the reservoir toward the free end 15 is stopped by the presence of the sterile filter 17.

[0086] The height H and the value of the angle α make it possible to determine a sufficient intensity value of the gravitational force that acts on the sufficient volume v.sub.s of eluent withdrawn so as to allow the flow of the sufficient volume of eluent through the segment 9.

[0087] Once the predetermined volume v of eluent is withdrawn from the reservoir, the valve is next positioned in its second position.

[0088] The eluent flows from the withdrawal segment 9 through the chromatographic column 3 according to an elution flow rate determined by the pressure drop of the chromatographic column 3.

[0089] The predetermined volume v of eluent is a sufficient volume V.sub.s to obtain, when the sufficient volume crosses under the action of a driving force of the eluent, which may for example be a drawing-off force of the eluent generated by a pump system connected to the outlet of the chromatographic column 3 at the determined elution flow rate, an eluate comprising a parent radioisotope activity comprised in a value range from 0.0% to 30.0% relative to a daughter radioisotope activity of said eluate. The parent radioisotope activity in the eluate is preferably comprised in a value range from 0.0% to 20.0%, more preferably from 0.0% to 10.0% relative to the daughter radioisotope activity of said eluate.

[0090] More preferably, the parent radioisotope activity is comprised in a value range from 0.0% to 5.0% relative to the daughter radioisotope activity of said eluate.

[0091] Still more preferably, the parent radioisotope activity is comprised in a value range from 0.0% to 2.0% relative to the daughter radioisotope activity of said eluate.

[0092] More advantageously, the parent radioisotope activity is comprised in a value range from 0.0% to 1.0% relative to the daughter radioisotope activity of said eluate.

[0093] Quite advantageously, the parent radioisotope activity is preferably equal to 0.0 mCi.

[0094] FIGS. 2a and 2b illustrate part of two separate alternatives of a second embodiment of the generator 1 according to the invention.

[0095] The second embodiment copies the features of the first embodiment and, additionally, a pumping means M.sub.P arranged to be connected hermetically to the eluate outlet 12. The pumping means M.sub.P can for example be a vacuum container.

[0096] Alternatively, the pumping means M.sub.P can be an actuator 18 comprising a piston 19 mounted in a cylinder 20 (FIG. 2a).

[0097] The cylinder 20 has a first end 21 communicating with the eluate outlet 12 of the chromatographic column 3.

[0098] The piston 19 is extended by an arm 22 that extends outside the cylinder 20 through an orifice 23 present on a second cylinder end 24, opposite the first cylinder end 21.

[0099] The piston has a first idle position R and a pumping position P (see FIG. 2b by equivalence).

[0100] During operation, after a first elution and before a second subsequent elution, the first valve 8 is kept in its second elution position and the pumping means M.sub.P is hermetically connected to the eluate outlet 12 while ensuring that the valve 8 is positioned in its second position.

[0101] Preferably, the eluate outlet is extended by a needle that is connected to a vacuum capsule by piercing a tight wall covering a fluid inlet orifice present on the capsule.

[0102] Once the needle penetrates the capsule, a residual volume of said eluent volume that is free, i.e., that is not retained in the stationary phase of the column, and that stagnates in the column, is automatically suctioned in the capsule.

[0103] By making it possible to evacuate this residual excess eluent volume present in the column, one thus minimizes the risk of having the parent radioisotope migrate toward the eluate outlet of the column between two successive elutions.

[0104] Once this free eluent is suctioned, ambient air is next expelled from the free end 15 or the segment 9 end 9′ of the second duct 7 so as to dry the excess eluent fraction.

[0105] The suctioning of the free eluent and the passage of air in the column therefore make it possible to bleed and dry the latter so as to obtain, between two elutions, a column that is dried or weakly impregnated with eluent.

[0106] Once the bleeding and drying of the column are done, the capsule is disconnected from the eluate outlet 12 and the eluate container 13 is once again connected to the column. Similarly to the vacuum capsule, the container comprises a tight wall designed to be crossed through by the needle positioned in the extension of the eluate outlet 12 of the column 3.

[0107] A new elution is next done first by positioning the first valve 8 in its first position to load the bypass segment 9 with eluent, and next by positioning the first valve 8 in its second elution position. This new elution is next followed by a new bleeding and drying step.

[0108] Thus, once a first elution is complete, the activity of the daughter radioisotope, which does not cease to be generated in the column from the parent radioisotope loaded on the column, increases to reach an activity threshold value that cannot be exceeded and that is governed by a secular equilibrium between the parent radioisotope and the daughter radioisotope. A cycle is thus formed, and it is the frequency between each successive elution (second, third, etc. elution) after the first elution that determines the respective parent and daughter radioisotope activities in the eluate obtained for each of these successive elutions.

[0109] Furthermore, the actuator 18 can be hermetically connected by a second valve 25 to the eluate outlet 12 (FIG. 2b).

[0110] The second valve 25 has an elution position in which the third duct 12′ is in fluid communication with the eluate container 13 via a fourth duct 12″ connecting the eluate container 13 to the valve, and a bleeding position in which the third duct 12′ is in fluid communication with the pumping means.

[0111] During operation, after a first elution and before a second subsequent elution, the second valve 25, initially in its elution position, is positioned in its bleed position, while the first valve 8 is kept in its second elution position. The piston is next set in motion between its first idle position R and its second pumping position P, which generates a pumping force of the remaining fraction of the sufficient volume of eluent.

[0112] The remaining fraction of the sufficient volume of eluent is therefore conveyed from the chromatographic column 3 toward the cylinder 20 of the actuator 18, which fills with eluent.

[0113] If the piston is kept in motion and when the free eluent is suctioned from the column, ambient air is next pumped from the free end 15 or the segment 9 end 9′ of the second duct 7 so as to drive the excess eluent fractions in order to obtain a column that is maximally impregnated with eluent.

[0114] Once the bleeding and drying of the column are done, the second valve 25 is positioned in its first position and a new elution is done by first positioning the first valve 8 in its first position to load the bypass segment 9 with eluent, and next by positioning the first valve 8 in its second elution position.

[0115] This new elution will next be followed by a new bleeding and drying step.

[0116] The generator according to a third embodiment (FIG. 3) further comprises a pressure switch 15′ connected to the free end 15 of the second duct or to the segment 9 end 9′.

[0117] In this third embodiment of the generator according to the invention, the pressure switch 15′ makes it possible to monitor the elution flow rate of the sufficient volume of eluent as well as a bleed flow rate, i.e., a pumping flow rate of the eluent, and a drying flow rate, i.e., a pumping flow rate of the air through the column, and to determine any operating anomalies of the generator.

[0118] For each of the embodiments of the generator described above, the choice of the sufficient predetermined volume is determined by the elution profile of the radioisotopes and therefore: (i) by the physicochemical properties of the chromatographic column and the eluent; (ii) and by the pair of parent and daughter radioisotopes used.

[0119] In reference to FIGS. 1 and 2, the present invention also pertains to an elution method for a chromatographic column 3 of a radioisotope generator 1 comprising an eluent reservoir 2 and connected to a chromatographic column 3 by a first eluent duct 4, said chromatographic column 3 having a stationary phase impregnated with eluent and loaded with a parent radioisotope disintegrating spontaneously into a daughter radioisotope.

[0120] The method according to the invention comprises the following steps: [0121] withdrawing a predetermined volume in a withdrawal segment 9 of a second eluent duct 7 connected to an upstream part 4′ of the first eluent duct 4 and a downstream part 4″ of the first eluent duct 4 by a valve 8, said withdrawal segment 9 being defined directly between the valve 8 and a segment end 9′. The withdrawal is done when the valve 8 is in a first position in which the second duct 7 is in fluid communication with said upstream part 4′ of the first eluent duct; and [0122] an elution step, under the action of a driving force of the eluent, of said predetermined volume of eluent from said withdrawal segment 9 toward said chromatographic column 3 when the valve 8 is in a second position in which the second duct 7 is in fluid communication with said downstream part 4″ of the first eluent duct 4.

[0123] The method further comprises a step for drying the column by pumping ambient air from the segment 9 and 9′ or from a free end 15 of the second duct 17 toward the eluate outlet 12.

[0124] The ambient air is sterilized by passing through the sterile filter 17 present on the second duct 7.

[0125] A bleeding step can be carried out before the drying step. This bleeding step is performed when the valve 8 is in its second position and after elution of the stationary phase of the chromatographic column 3 by the sufficient volume of eluent, which consists of pumping a remaining fraction of the sufficient volume of eluent present in column 3.

[0126] In this method, the predetermined volume of eluent is a sufficient volume to obtain, when the sufficient volume crosses through the chromatographic column 3, an eluate comprising a parent radioisotope activity comprised in a value range from 0.0% to 30.0% relative to a daughter radioisotope activity of the eluate.

[0127] Preferably, the method comprises a step for blocking the eluent, after said injection step, so as to block the passage of said eluent volume past said segment end 9′.

[0128] The blocking step is ensured by the presence of a sterile filter 17 with a polarity opposite that of the eluent whose function is to allow air to pass in the bypass segment 9 and to block the passage of the eluent in a defined direction from the end 7′ of the connected part of the second duct 7 toward the segment end 9′.

[0129] The method according to the invention makes it possible preferably to obtain a parent radioisotope activity that is comprised in a value range from 0.0% to 20% relative to the daughter radioisotope activity of said eluate.

[0130] Advantageously, the parent radioisotope activity is comprised in a value range from 0.0% to 10% relative to the daughter radioisotope activity of said eluate.

[0131] More preferably, the parent radioisotope activity is comprised in a value range from 0.0% to 5.0% relative to the daughter radioisotope activity of said eluate.

[0132] Still more preferably, the parent radioisotope activity is comprised in a value range from 0.0% to 2.0% relative to the daughter radioisotope activity of said eluate.

[0133] More advantageously, the parent radioisotope activity is comprised in a value range from 0.0% to 1.0% relative to the daughter radioisotope activity of said eluate.

[0134] Advantageously, the parent radioisotope activity is equal to 0.0 mCi.

[0135] The results relative to the operation of the generator according to the present invention are described below for illustrative purposes and should in no way be considered limiting.

[0136] These results are relative to loading and elution tests of the generator according to the invention for different parent/daughter radioisotope pairs and different stationary phases.

[0137] Operational Mode

[0138] Loading of the Generator

[0139] Test 1 pertains to the .sup.99Mo/.sup.99mTc pair (parent/daughter) on a first titanium-based stationary phase of a first generator according to the invention done in aqueous phase with an acid pH. The activity loaded on the stationary phase was 27.9 mCi during the loading time T.sub.0.

[0140] Test 2 pertains to the .sup.99Mo/.sup.99mTc pair and a second aluminum-based stationary phase of a second generator according to the invention done in aqueous phase with an acid pH. The activity loaded of the stationary phase was 57.8 mCi at the loading time T.sub.0.

[0141] Elution Test

[0142] For tests 1 and 2, the reservoir consists of a pouch of NaCl saline solution concentrated at 0.9 vol %.

[0143] The two generators were diluted daily for a determined period in order to monitor the elution performance and the release rates of .sub.99Mo in each of the eluates withdrawn daily (breakthrough).

[0144] Results

[0145] The elution performance Y (in %) is understood in the context of the present invention as the ratio of the activity of the .sup.99mTc [A(.sup.99mTc).sup.el in mCi] in the eluate and the activity of the .sup.99mTc [A(.sup.99mTc.sup.col mCi] that is present on the column at the time of the elution and is calculated using the following formula:

Y(in %)=100×[A(.sup.99mTc).sup.el/A(.sup.99mTc).sup.col]

[0146] The .sup.99Mo release rates are given in % and correspond of the following ratio:

[0147] R=100×[A(.sup.99Mo).sup.el/A(.sup.99mTc).sub.el], where A(.sup.99Mo).sup.el represents the .sup.99Mo activity in the eluate.

[0148] The results relative to tests 1 and 2 are provided in tables 1 and 2 below:

TABLE-US-00001 TABLE 1.0 .sup.99Mo/.sup.99mTc pair on TiO.sub.2 - test 1 Time T Y (in %) R (%)* T.sub.0 99 <1.4 10.sup.−6 T.sub.0 + 1 day 91 <1.6 10.sup.−6 T.sub.0 + 2 days 93 <2.0 10.sup.−6 T.sub.0 + 8 days 95 <1.9 10.sup.−6 T.sub.0 + 9 days 95 <3.2 10.sup.−7 T.sub.0 + 10 days 95 <1.4 10.sup.−6 T.sub.0 + 11 days 97 <1.6 10.sup.−6 T.sub.0 + 13 days 94 <6.4 10.sup.−6 T.sub.0 + 14 days 96 <6.9 10.sup.−6 T.sub.0 + 15 days 98 <6.8 10.sup.−6 T.sub.0 + 16 days 98 <7.1 10.sup.−6 T.sub.0 + 17 days 95 <9.0 10.sup.−6 T.sub.0 + 21 days 94 <3.0 10.sup.−6 T.sub.0 + 22 days 94 <2.1 10.sup.−6 *The specifications of the European pharmacopeia (Monographs for sodium pertechnetate (.sup.99mTc) for injection produced by fission “Eur. Phar. 0124” and Monographs for sodium pertechnetate (.sup.99mTc) for injection not produced by fission “Eur. Phar. 0283”) provide a threshold value not to be exceeded of approximately 0.1%.

TABLE-US-00002 TABLE 2 .sup.99Mo/.sup.99mTc pair on Al.sub.2O.sub.3 - test 2 Time T Y (in %) R (in %)* T.sub.0 92 <4.4 10.sup.−4 T.sub.0 + 1 day 100 <3.1 10.sup.−4 T.sub.0 + 2 days 100 <2.3 10.sup.−4 T.sub.0 + 3 days 100 <1.2 10.sup.−4 T.sub.0 + 6 days 100 <3.3 10.sup.−4 T.sub.0 + 7 days 101 <4.5 10.sup.−5 T.sub.0 + 9 days 99 <2.8 10.sup.−4 T.sub.0 + 10 days 101 <6.3 10.sup.−5 T.sub.0 + 13 days 99 <5.0 10.sup.−5 T.sub.0 + 14 days 99 <2.7 10.sup.−5 *The specifications of the European pharmacopeia (Monographs for sodium pertechnetate (.sup.99mTc) for injection produced by fission “Eur. Phar. 0124” and Monographs for sodium pertechnetate (.sup.99mTc) for injection not produced by fission “Eur. Phar. 0283”) provide a threshold value not to be exceeded of approximately 0.1%.

[0149] Based on tests 1 and 2 and a reference test, the values illustrated in Table 3 are found:

TABLE-US-00003 TABLE 3 Pair // stationary phase Y (in %) R (in %)* .sup.68Ge/.sup.68Ga // TiO.sub.2.sup.§  >70%.sup.§§§   10.sup.−4-10.sup.−6§§§§ .sup.99Mo/.sup.99mTc // TiO.sub.2.sup.§§  ~95% ~10.sup.−6-10.sup.−7 .sup.99Mo/.sup.99mTc // Al.sub.2O.sub.3.sup.§§ ~100%   10.sup.−4-10.sup.−5 .sup.§Values measured at time T = T.sub.0 .sup.§§Average values .sup.§§§Y (in %) = 100 × [A(.sup.68Ga).sup.el/A(.sup.68Ge).sup.col] .sup.§§§§R = 100 × [A(.sup.68Ge).sup.el/A(68.sup.Ga).sup.el], where A(.sup.68Ge).sup.el represents the activity of .sup.68Ge in the eluate. *The specifications of the European pharmacopeia (Monographs for sodium pertechnetate (.sup.99mTc) for injection produced by fission “Eur. Phar. 0124”; Monographs for sodium pertechnetate (.sup.99mTc) for injection not produced by fission “Eur. Phar. 0283” and Monographs for “Gallium solution (.sup.68Ga) (Chloride) for radioactive labeling” “Eur Phar 2464”) provide a threshold value not to be exceeded of approximately 0.1%.

[0150] As shown by the results provided above, the parent radioisotope activity detected in the eluate is on average lower by a factor of 10.sup.−6 -10.sup.−8 relative to the daughter radioisotope activity in the same eluate, which means a parent radioisotope activity of less than 1.0% relative to the daughter radioisotope activity of the eluate, which is quite remarkable.

[0151] Of course, the present invention is in no way limited to the embodiments described above, and changes may be made thereto without going beyond the scope of the appended claims.

[0152] For example, the generator according to the present invention may be used in applications other than use for pharmaceutical or medical purposes.

[0153] Furthermore, although the description discloses a generator comprising a valve, it is understood that the present invention is not limited to a generator comprising only one valve, but also covers other embodiments in which several valves fluidly connect the withdrawal segment to the reservoir and the column.

[0154] As an illustration, a fourth embodiment in which the generator comprises a first valve connecting the withdrawal segment to the reservoir and a second valve connecting the same segment to the chromatographic column can of course be considered as an equivalent implementation of the generator according to the invention.