MXPA00011635A - Method for sequential injection of liquid samples for radioisotope separations - Google Patents

Abstract

The present invention is a method of separating a short-lived daughter isotope from a longer lived parent isotope, with recovery of the parent isotope for further use. Using a system with a bi-directional pump and one or more valves, a solution of the parent isotope is processed to generate two separate solutions, one of which contains the daughter isotope, from which the parent has been removed with a high decontamination factor, and the other solution contains the recovered parent isotope. The process can be repeated on this solution of the parent isotope. The system with the fluid drive and one or more valves is controlled by a program on a microprocessor executing a series of steps to accomplish the operation. In one approach, the cow solution is passed through a separation medium that selectively retains the desired daughter isotope, while the parent isotope and the matrix pass through the medium. After washing this medium, the daughter is released from the separation medium using another solution. With the automated generator of the present invention, all solution handling steps necessary to perform a daughter/parent radionuclide separation, e.g. Bi-213 from Ac-225"cow"solution, are performed in a consistent, enclosed, and remotely operated format. Operator exposure and spread of contamination are greatly minimized compared to the manual generator procedure described in U.S. patent application 08/789,973 herein incorporated by reference. Using (16) mCi of Ac-225, there was no detectable external contamination of the instrument components.

Description

METHOD OF SEQUENTIAL INJECTION OF LIQUID SAMPLES FOR SEPARATIONS OF RADIOISOTOPES FIELD OF THE INVENTION The present invention relates generally to the chemical separation of radionuclides. More specifically, it refers to an automated chemical separation method of one radionuclide from another, and more specifically, it refers to the automation of the separation of a short-lived child isotope, from a parent isotope of life plus long, where the isotope son is useful in nuclear medicine. BACKGROUND OF THE INVENTION The separation of short-lived alpha and beta emitting radionuclide isotopes from long-living parent isotopes has been made for medical treatment, especially against cancer. The widespread recognition of the use of radiation to annihilate or neutralize unwanted cell growth, such as cancer, has led to an increasing interest in different radionuclide species. Of particular interest are radionuclides, such as 213Bi, which emit alpha radiation, or alpha emitters, because the alpha radiation emitted by these radionuclides does not penetrate deeply into the tissue. 213Bi is normally produced as a child product of 229Th (t1 / 2 = 7300 years).

The chain of radioactive decay where 213Bi is found is well known: 233U (1.62 x 105 years t1 / 2) at 229Th at 225Ra (14.8 days t1 / 2) at 2 5Ac (10 days t1 / 2) at 213Bi (47 minutes) t1 / 2). Children of interest for biological applications include 225Ra that decays to 225Ac. In turn, 225Ac decays through a series of steps up to 213Bi (t1 / 2 = 45.6 minutes). Briefly, by placing alpha emitters adjacent to unwanted cell growth, such as a tumor, the tumor can be exposed to alpha radiation without undue exposure of surrounding healthy tissue. In many of these schemes, the alpha emitter is placed adjacent to the tumor site by linking the alpha emitter with a chelator, which in turn binds with a monoclonal antibody, which will look for the site of the tumor inside the body. Unfortunately, in many cases, the chelator will also bond with metals other than the desired alpha emitter. Accordingly, it is desirable that the number of monoclonal antibodies bound to metals other than the desired alpha emitter be minimized. Therefore, it is desirable that the alpha emitter be highly purified of other metal cations. In addition, alpha emitters, such as 213Bi (47 minutes t12) have very short half-lives. Therefore, to use these short-lived radionuclides effectively in medical applications, they must be efficiently separated from other metals or contaminants in a short period of time to maximize the amount of available alpha emitter. Moreover, there are emissions-? Low abundance and low energy associated with 13Bi, which are useful for the imaging of patients. A more detailed description of the use of these radionuclides can be found in numerous articles, including Pippin, C. Greg, Otto A. Gansow, Martin W. Brechbiel, Luther Koch, R. Molinet, Jaques van Geel, C. Apostolidis, Maurits W. Geerlings, and David A. Scheinberg. 1995. "Recovery of Bi-213 from an Ac-225 Cow: Application to the Radiolabeling of Antibodies with Bi-213", Chemists1 Views of Imaging Centers, Edited by A.M. Emran, Plenum Press, New York, NY (Pippin, 1995). In 1996, Dr. David Scheinberg of Memorial Sloan-Kettering Cancer Center, New York, NY, began administering 213Bi to a patient for the treatment of acute leukemia. 213Bi is an alpha emitter that can bind to a monoclonal antibody, "a designed protein molecule" that, when attached to the outside of the cell membrane - can supply radioactive 213Bi, an alpha emitter with a half-life of 47 minutes . This initial trial represented the first use of alpha therapy for the treatment of human cancer in the United States. Different methods have been developed to separate bismuth from other radionuclides over the past years. Recent work designed to develop Bi generators has focused on the use of an organic cation exchange resin loaded with actinium (Pippin, 1995).; Wu, C, M.W. Brechbiel, and O.A. Gansow. 1996. An Improved Generator for the Production of Bi-213 from Ac-225, American Chemical Society Meeting, Orlando, Fl, August 1996 (Wu, 1996); and Mirzadeh, S., Stn J. Kennel, and Rose A. Boíl. 1996 Optimization of Radiolabeling of Immunoproteins with Bi-213, American Chemical Society Meeting, Orlando, Fl. August 1996). The main problem with the organic cation exchange method is that, with the need for larger quantities of 225Ac of "cow" or of origin (> 20 mCi), the generator is limited by the early destruction of the exchange resin. Organic cations loaded with actinium. Attempts to minimize this destruction have been employed by Dr. Wu at the National Institute of Health (Wu, 1996), and Dr. Ron Finn (Finn, R., M. McDevitt, D. Scheinberg, J. Jurcic, S. Larson, G. Sgouros, J. Humm, and M. Curcio (MSKCC), M. Brechbiel and 0. Ganzow (NIH), M. Geerlings, Sr. (Pharmactinium Inc., Wilmington, DE); and C. Apostolidis, and R. Molinet (European Commission, Joint Research Center, Institute for Transruanium Elements, Karlsruhe, FRG.). 1997. "Refinements and Improvements for Bismuth-213 Production and Use as Targeted Therapeutic Radiopharmaceuticals", J. Labelled Compounds and Radiopharmaceuticals, XL, page 293 (MSKCC, 1997)). Instead of loading the 225Ac as a "point" source on the upper surface of a cation exchange column (Karlsruhe approach), the actinium is exchanged on a portion of the organic resin in a batch mode. Then the charged ion exchange beads are mixed with the uncharged beads to "dilute" the destructive effect, when placed on an ion exchange column used for the separation of Bi. The 213Bi eluting from the generator is chemically reactive, and radiolabelling efficiencies with antibodies greater than 80 percent are easily reached (corrected decay). The entire process, including radiolabelling of the monoclonal antibody, takes place at room temperature within 20 to 25 minutes. The immunoreactivity of the product has been determined at a nominal value of 80 percent. The resulting radiopharmaceutical is free of pyrogen and is sterile. However, under this approach, preparation of the "cow" or sample before Bi separation of the organic resin is delayed, and may not meet the ALARA radiation standards. In addition, 225Ac remains associated with the organic resin during the lifetime of the generator (approximately 20 days), releasing organic fragments to the solution of the 213Bi product each time the cow is milked or the sample is obtained. The Karlsruhe radionuclide generator described in Koch, 1997, was developed in support of Dr. David Scheinberg (Memorial Soan-Kettering Cancer Center (MSKCC), New York, NY) who linked 213Bi with a recombinant humanized antibody M195 (HuM 195 ). All 225Ac was loaded on an inlet edge of an AGMP-50 cation exchange resin column. Due to radiation damage to the ion exchange column and to the resin, the MSKCC altered the Karlsruhe radionuclide generator to extend 2 5Ac through the entire resin bed. This alteration reduced the damage by local radiation, but because 225Ac remains in the resin, the resin suffers damage by alpha activity. A concept of "generator" of inorganic ion exchange has been developed by Gary Strathearn, Isotope Products Laboratories, Burbank, CA and is described (Ramírez Ana R. and Gary E. Strathearn, 1996. Generator System Development of Ra-223, Bi -212, and Bi-214 Therapeutic Alpha-Emitting Radionuclides, American Chemical Society Meeting, Orlando, Fl. August 1996 (Ramirez, 1996). In this approach, inorganic polyfunctional cation exchangers are used to avoid the damage of the intense alpha bombardment. A column of Alphasept 1MR is previously treated with nitric acid (HN03), then the 225Ac in the 1M HN03 feed is loaded onto the column the 213Bi product is eluted with the 1M HN03. The HN03 product must then be evaporated to dryness to remove the nitric acid. Then we return to the solution with a suitable regulated solution to prepare the final link of the alpha emitter with a chelator and a monoclonal antibody. The evaporation step prolongs the time required to prepare the final product, and limits the usefulness of this approach. An anion exchange bismuth separator and method was developed as described in United States Patent Application Number 08 / 789,973. The method requires the manual operation of syringes, and therefore, has the drawback of needing technical manpower, with the inherent possibility of a radioactive exposure for the worker. Due to the need for increasing amounts of therapeutic radionuclides, there is a need for a method for the rapid and safe separation and purification (low operator exposure) of daughter radioisotopes from parent radioisotopes, for example 213Bi from 229Th. SUMMARY OF THE INVENTION The present invention is a method of separating a short-lived child isotope from a parent isotope of longer life, with the recovery of the parent isotope for further use. Using a system with a bidirectional pump and one or more valves, a solution of the parent isotope is processed to generate two separate solutions, one of which contains the isotope son, from which the parent has been removed with a high decontamination factor, and the other solution contains the recovered parent isotope. The process can be repeated on this solution of the parent isotope. The system with the fluid impulse and one or more valves is controlled by a program in a microprocessor that executes a series of steps to perform the operation. In one approach, the cow or origin solution is passed through a separation means that selectively retains the desired child isotope, while the parent isotope and the matrix pass through the medium. After washing this medium, the son is released from the separation medium using another solution. With the automated generator of the present invention, all of the solution handling steps necessary to perform a daughter / parent radionuclide separation, for example, Bi-213 from the "cow" solution or from Ac-225 origin, are carried out in a consistent, enclosed, and remotely operated device. The exposure of the operator and the extent of contamination are greatly minimized, as compared to the manual generator method described in United States Patent Application Number 08 / 789,973, incorporated herein by reference. Using 16 mCi of Ac-225, there was no detectable external contamination of the instrument components. It is an object of the present invention to separate and purify a shorter-lived isotope of a longer living parent isotope in an automated system, recovering the parent isotope for future use. It is an object of this invention that the parent isotope can be reused to recover more isotope son at a later time, without manual manipulation of the parent isotope involved. It is an object of this invention that the radiolytic exposure of the separation medium is minimized. The subject matter of the present invention is particularly pointed out and distinctly claimed in the concluding portion of this specification. However, both the organization and the method of operation, together with the advantages and additional objects thereof, can be better understood by reference to the following description, taken in conjunction with the accompanying drawings, wherein the like reference characters are refer to the same elements. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram of the apparatus of the present invention, with separate valves. Figure 2 is a schematic diagram of the apparatus of the present invention, with a multi-position valve. Figure 3a is a schematic diagram of an apparatus of the system of the present invention, with two multi-position valves and a separator. Figure 3b is a schematic diagram of the system apparatus as in Figure 3a, but with an optional two position valve. Figure 4a is a plot of the activity against the elution profile of the eluent volume (Example 1). Figure 4b is a graph of the percentage of Bi recovered against the volume of eluent (Example 1). Figure 5a is a plot of the activity against the elution profile of the eluent volume (Example 3). Figure 5b is a graph of the percentage of Bi recovered against the volume of eluent (Example 3). DESCRIPTION OF THE PREFERRED MODALITIES The apparatus of the present invention is shown in Figure 1. A bidirectional pump 100 is connected to a pipe segment 102. The bidirectional pump 100 and the pipe segment 102 are filled with a regulating liquid (not shown).

A first valve 104 is connected to the pipe segment 102, and is connected with a gas supply (not shown), to put a volume of a gas in contact with the regulating liquid. A second valve 106 is connected to the pipe segment, allowing to direct a first sample of liquid (not shown) of a mixture of the short-lived child isotope and the long-lived parent isotope in the pipe segment, removing a quantity of regulating liquid . The first liquid sample is prevented from contacting the regulating liquid by the volume of gas between them. The size (internal diameter) of the segment of pipe and other pipes is selected in such a way that the surface tension of the liquids in cooperation with the internal diameter is sufficient in the presence of a gas to prevent the flow of the liquid passing through the gas. Isolation valves 108 can be included. Because additional currents are required, for example the wash stream, the eluent stream, the waste stream, the reagent stream, for a complete operation of a separation system, it is preferred that the valves 104, 106, and other connected ones are connected to the pipe segment 102 so that additional currents are collected in a multi-position valve 200, as shown in Figure 2. In Figure 3a a complete system for Separate Bi-213 from Ac-225. The bidirectional pump 100 is a high precision digital syringe pump (syringe volume of 10 milliliters) (Alitea EUA, Medina WA). The pipe segment 102 is a coil connected to a first multi-position valve 200 that contains the gas valve or gate 104, the sample or cow valve or gate 106, and others, as shown. An outlet gate 300 directs the fluids to a separator 302. The outlet of the separator is connected to a second multi-position valve 304. A cow or sample tank 306 is connected to the gates on both the first and second valves. multiple positions. A product tank 308 collects the desired radionuclide solution. To separate the Bi-213 from the Ac-225, the separator 302 is an anion exchange membrane. In Figure 3b there is shown an alternative embodiment including a two position, four gate valve 310. In this embodiment, the first multi position valve 200 is connected to a separator reactor gate (two position valve 310, gate 1), and a stack of zones is provided from the pipe segment 102 through the two position valve 310 to the separator 302 at a specific flow rate. The purpose of the two position valve 310 is to provide the possibility of reversing the flow direction through the separator 302. The two position valve 310 is optional. A preferred material for separation is an anion-absorbing resin in the form of a membrane system, provided by 3M, St. Paul, MN. The membrane system has a thin organic paper membrane containing the anion exchange resin incorporated in a cartridge. The anion exchange resin, AnexF, from Sarasep Corp. Santa Clara, CA, is milled to a powder, and secured in a PTFE (polytrifluoroethylene) membrane according to the method described in the US Pat. North American 5,071,610 of 3M, incorporated herein by reference. For our test, the cartridge was 25 millimeters in diameter. Both the size of the cartridge and the type of anion exchange resin used can be varied, depending on the size required by the generator. In an alternative way, the anion exchange resin can be in the form of particles placed in a column. The size of the cartridge or the column can be determined by the desired exchange capacity. All valves are preferably non-metallic, for example, Cheminert ™ obtained from Valco Instrument Company, Inc., (Houston TX). Also, the reagent and transport lines, including the pipe segment 102, are preferably non-metallic and chemically inert, for example, polytetrafluoroethylene (Teflon), polyvinylidene fluoride resin (Kynar), polyetherethylketone (PEEK) and combinations thereof. The pump and valves are controlled remotely from a microprocessor. Any microprocessor and operating software can be used, for example, a lap-top personal computer using the FIALAB software (Alitea). The method of the present invention is to separate a short-lived child isotope from a long-lived progenitor isotope, and has the steps of: (a) filling a connected bidirectional pump, and a segment of tubing connected thereto, with a regulating liquid; (b) placing a volume of a gas in contact with the regulating liquid, removing a first quantity of the regulating liquid; and (c) directing a first sample of liquid from a mixture of the short-lived child isotope and the long-lived progenitor isotope to the pipe segment, removing a second quantity of regulating liquid, wherein the first liquid sample is separated from the liquid regulator by the volume of the gas. For the separation of the daughter radionuclides of the parent radionuclides, the details of these steps as well as the additional steps are system initialization (in sequence), separator conditioning, debugger loading and source or cow solution and supply through the separador, and pickup of the son. Specifically, a Bi generator can have, as the starting material, either 225Ac, separated from the progenitors, or a mixture of 225Ra / 225Ac. There are advantages and disadvantages to the use of 225Ra as a starting material. If the 225Ra does not separate from the 225Ac, the amount of Bi in terms of radioactivity available as a function of time is greatly extended. However, if the 225Ra also contains a fraction of 224Ra, because the original thorium source or "cow" solution contained both 229Th and a small percentage of 228Th, separation to remove the radium is desirable. The apparatus of the present invention can be used in two modes, in stacking, and in sequence. The stacking mode has multiple "sludges" of liquid separated by multiple "sludges" of gas, while the sequential mode has only one "sludge" of gas to separate the "sludge" charged in liquid sequence, from the regulating liquid . For the separation of Bi-213 from Ac-225 (without 225Ra), the steps using the apparatus of the present invention are: 1. Initialization of the System (in sequence). 1.1 Valve 200 in the waste position (gate 7). The syringe is emptied at 10 milliliters / minute. 1.2 0.250 milliliters of the air segment are sucked into the containment coil at 10 milliliters / minute. This step was used to ensure that only the air segment is present in the containment coil and in the main line of the multi-position valve A before the solution is supplied. This step eliminates any potential for contamination of the reactive solutions with the carrier solvent, and was used as a precaution. 2a. Conditioning of the separator (stacked). 2a.1. gas, preferably air, is withdrawn or pulled into the pipe segment 102 through the valve 104 (gate 1 in the first multi-position valve 200), preferably at a flow rate of about 2 milliliters to about 10 milliliters / minute. 2a.2. a membrane conditioning reagent (same as the liquid containing the source solution or "cow" but without the source solution or "cow") is directed into the pipe segment 102 through the valve 200, gate 2, preferably 4 milliliters of 0.5 HCl, at a flow rate of 10 milliliters / minute. 2a.3. the membrane conditioning agent is expelled from the pipe segment 102, through the separator 302 (valve 200, gate 6) towards the waste (valve 304, gate 6), followed by air, preferably approximately 1.9 milliliters of air at a rate flow rate of approximately 4 milliliters / minute. Direction of flow: flow down (in Figure 3b, gates 1 and 2 in the two-way valve are connected). 2a.4. The valve 200 is switched to waste (gate 7), and the remaining air is expelled (approximately 0. 1 milliliter) of the pipe segment 102 to the waste, followed by 0.5 milliliter of the carrier solution. The flow rate of preference is about 10 milliliters / minute. The carrier solution is a liquid that does not wet the pipe and / or the internal surfaces of the valve. The preferred carrier solution is deionized water. For clinical applications, the carrier solution can be a sanitizing solution (e.g., 50-80 percent ethanol solution). By using the ethanol solution as a carrier solution, the generating instrument can be kept sterile. By washing the tubing with ethanol, its tendency to moisten is minimized. At this point, the separator 304 is conditioned and ready for separation. All transport lines and separator 304 are filled with air. 2b. Conditioning of the separator (in sequence) 2b.1. Gas, preferably air, is drawn into the pipe segment 102 through the valve 200, gate 1, preferably about 1 milliliter, at a flow rate of about 18 milliliters / minute. 2b.2. The membrane conditioning reagent is sucked from the valve 200, gate 2, into the pipe segment 102, preferably about 4 milliliters of HCl about 0.5, at a flow rate of about 18 milliliters / minute. 2b.3. The membrane conditioning reagent is expelled from the pipe segment 102, through the separator 302 (valve 200, gate 6), to the waste (valve 304, gate 6), followed by air, preferably about 1 milliliter, with a flow rate of about 8 milliliters / minute. Direction of flow: flow down (gates 1 and 2 in the 2-way valve 310 (Figure 3b) are connected 2b.4 Air is drawn through valve 200, gate 1, into the pipe segment 102, preferably about 10 milliliters, at a flow rate of about 18 milliliters / minute 2b.5 The valve 200 is switched to the membrane position (gate 6) Approximately 10 milliliters of air are expelled through the separator 302, at a flow rate of approximately 15 milliliters / minute, to the waste (valve 304, gate 6) 3a.Filling and supplying the "cow" or source and purifier solutions to the pipe segment (stacked) Debugger load and "cow" or source solution (stacked) 3a.1. Air is drawn into pipe segment 102 through valve 200, gate 1, preferably about 2 milliliters, at a flow rate of about 10 milliliters / minute. 3a.2. The treatment solution is drawn into the pipe segment 102 through the valve 200, gate 4, preferably about 4 milliliters of HCl about 0.005 M, at a flow rate of about 10 milliliters / minute. 3a.3. Air is drawn into pipe segment 102, preferably about 2 milliliters, at a flow rate of about 10 milliliters / minute. 3a.4. The "cow" or source solution is directed through the valve 200, gate 5, into the pipe segment 102, preferably about 4 milliliters, at a flow rate of about 4 milliliters / minute. Note that the volume of "cow" or source solution is only about 3 milliliters. The aspiration of a volume of approximately 4 milliliters ensures the quantitative transfer of the cow or origin solution into the pipe segment 102. At this point, the pipe segment 102 contains the stacked areas in sequence of the "cow" solutions. "or of origin and purifier, separated with the air segments. In an alternative way: Supply of "Cow" or Origin Solution and Debugger (stacked) 3a.5. The multi-position valve 304 is in the "cow" or origin (gate 1) position. 3a.6. The multi-position valve 200 is in the membrane position (gate 6). 3a.7. The 2-position valve 310 (optional) is switched to the upstream position (gates 1 and 4 are connected). 3a.8. "Cow" or source and air solution (preferably approximately 1.8 milliliters) are supplied to separator 302, and the effluent is directed towards the "cow" storage container or original solution 306 through valve 304 (gate 1). This step is performed by dosing approximately 6,350 milliliters from the containment coil at a flow rate of 4 milliliters / minute. (Note that the actual volumes and dosed volumes are different.) The dosed volumes were found experimentally in cold tests, and take into account the elasticity of the air segments stacked in the containment coil. solution was not affected). 3a.9. The multi-position valve 304 is in the debugger position (gate 2). 3a.10. The purifying solution (preferably about 4 milliliters of HCl about 0.005 M) and air (preferably about 1.9 milliliters) are supplied to the separator 302, and directed to the valve 304 (gate 2). The purifying fraction is collected for subsequent analysis. 3a.11. The valve 200 is switched to the waste (gate 7) ejects the remaining air (approximately 0.1 milliliters) from the containment coil to the waste, followed by the carrier solution (approximately 0.5 milliliters). The flow rate is preferably about 10 milliliters / minute. At this point, Bi-213 is retained on the anion exchange membrane inside the separator 302, and is separated from the parent Ac-225. The "cow" or source Ac-225 solution is recovered in the original storage container 306. The separator 302 and the transport lines are flooded with air. Separator 302 is ready for elution of Bi-213. 3b. Loading and supply of solutions of "cow" or origin and purifier to the pipe segment (in sequence). Loading and Supply of "Cow" or source solution (in sequence) 3b.1. Air is drawn through valve 200, gate 1, into pipe segment 102, preferably about 1 milliliter, at a rate of about 10 milliliters / minute. 3b.2. The valve 200 is switched to the position of "cow" or solution of origin (gate 5). Approximately 4 milliliters of cow or source solution is directed into the pipe segment 102 at a flow rate of approximately 4 milliliters / minute. The volume of "cow" solution or source of Ac-225 is nominally 3.1 milliliters.

The aspiration of approximately 4 milliliters ensures the quantitative transport of the "cow" or source solution into the pipe segment 102. 3b.3. The operator is asked to confirm the additional procedure with automated separation. 3b.4. The valve 200 is switched to the membrane position (gate 6). The valve 304 is switched to the return position of "cow" or source solution (gate 1). The two-position valve 310 is switched to the upstream flow position (gates 1 and 4 are connected). 3b.5. About 5 milliliters are expelled from the pipe segment 102 to the cow storage tank or source solution 306 (valve 304, gate 1) at a flow rate of about 4 milliliters / minute. The "cow" or source Ac-225 solution is propelled through the separator 302, and returned to the storage vessel 306. 3b.6. The valve 200 is switched to the "air" position (gate 1). Approximately 10 milliliters of air is drawn into the pipe segment 102, at a flow rate of approximately 8 milliliters / minute. 3b.7. The valve 200 is switched to the membrane position (gate 6). The two-position valve xx is switched to the downstream position (gates 1 and 2 are connected). 3b.8. About 10 milliliters of air is expelled from the pipe segment 102 to the "cow" storage container or source solution 306 through the valve 304, gate 1, at a flow rate of approximately 15 milliliters / minute. At this point, the Bi-213 is loaded into the separator 302, and the Ac-225 solution is returned to the original storage vessel 306. Debugger Supply and Delivery (in sequence) 3b.9. The valve 200 is switched to the air position (gate 1). The valve 304 is switched to the debugger position (gate 2). 3b.10. Air is drawn into the pipe segment 102 through the valve 200, gate 1, preferably about 1 milliliter, at a flow rate of about 10 milliliters / minute. 3b.11. The valve 200 is switched to the scrubber position (gate 4). About 4 milliliters of the treatment solution is drawn into the pipe segment 102, at a flow rate of approximately 20 milliliters / minute. 3b.12. The valve 200 is switched to the membrane position (gate 6). About 5 milliliters are expelled from the pipe segment 102 through the separator 302 to the debugger position of the valve 304, gate 2, at a flow rate of approximately 6 milliliters / minute (direction of flow up through the separator 302). 3b.13. The valve 200 is switched to the "air" position (gate 1). Approximately 10 milliliters of air are drawn into the pipe segment 102, at a flow rate of approximately 18 milliliters / minute. 3b.14. The valve 200 is switched to the separator position. Approximately 10 milliliters of air are expelled from the pipe segment 102 to the waste (valve 304, gate 6), at a flow rate of approximately 15 milliliters / minute. 4. a Bi-213 elution sequence (stacking) 4a.1. The two-position valve is switched 310. The flow direction is reversed through the separator 302 for the elution of the Bi-213 (flow down, gates 1 and 2 in the two position valve 310 are connected). Note that the direction of flow through separator 302 is reversed in relation to the loading and debugging (washing) steps of the Ac-225. 4a.2. The multi-position valve 304 is established in the product position of Bi-213 (gate 3). 4a.3. An air segment is pulled inward from the pipe segment 102 through the valve 200, gate 1, preferably about 2 milliliters, at a flow rate of approximately 10 milliliters / minute. 4a.4. Eluent is drawn into pipe segment 102 through valve 200, gate 3, preferably a portion of about 8 milliliters of sodium acetate about 0.1 M, at a flow rate of about 18 milliliters / minute. 4a.5. The eluent of the pipe segment 102 is expelled through the separator 302 (valve 200, gate 6) to the product container 306 (valve 304, gate 3), preferably about 8 milliliters of sodium acetate about 0.1 M, to a flow rate of approximately 1 milliliter / minute. 4a.6. Air is dosed, preferably about 1.9 milliliters, at a flow rate of about 4 milliliters / minute. 4a.7. The valve 200 is switched to waste (gate 7), and the remaining air (approximately 0.1 milliliters) is expelled from the pipe segment 102 to the waste, followed by approximately 0.5 milliliters of carrier solution. The flow rate is approximately 10 milliliters / minute.

At this point, the Bi-213 product is eluted from the anion exchange membrane in the separator 302, and it is collected in the product container 306. The separator 302 and all the transport lines are flooded with air. The system is ready for the next separation. 4b. Elution sequence of Bi-213 (in sequence) 4b.1. The valve 200 is switched to the air position (gate 1). The valve 304 is switched to the product position (gate 3). 4b.2. Air is drawn into the pipe segment 102 through the valve 200, gate 1, preferably about 1 milliliter, at a flow rate of about 10 milliliters / minute. 4b.3. The valve 200 is switched to the eluent position (gate 4). Approximately 4 milliliters of NaOAc approximately 0.1M are pulled into the pipe segment at a flow rate of approximately 20 milliliters / minute. 4b.4. The 2-position valve 310 is switched to the downstream position (gates 1 and 2 are connected). Note that the direction of flow is opposite in relation to the loading steps of Ac-225 and membrane debugging (washing). 4b.5. The valve 200 is switched to the separator position (gate 6). About 5 milliliters are expelled from the pipe segment 102 through the separator 302 to the product container 308 (valve 304 gate 3), at a flow rate of about 1 milliliter / minute (downstream flow direction). 4b.6. The valve 200 is switched to the "air" position (gate 1). Approximately 5 milliliters of air are drawn into the pipe segment 102, at a flow rate of approximately 18 milliliters / minute. 4b.7. The valve 200 is switched to the separator position. Approximately 5 milliliters of air are expelled from the pipe segment 102 to the product container 308 (gate 3, valve 304), at a flow rate of approximately 15 milliliters / minute. After the membrane is replaced, or possibly washed to reuse, the instrument is ready to proceed with the next separation. Experimental Equipment and Procedure All reagent and transport lines were constructed of FEP teflon tubing with an internal diameter of 0.8 millimeters (Upchurch Scientific, Oak Harbor WA). The containment coil was made of FEP pipe with an internal diameter of 1.6 millimeters (Upchurch). The length of the pipe segment 102 was 6.25 meters (calculated volume of 12.5 milliliters), and wound on a coil. The purpose of the pipe segment 102 is to accommodate the reagent solutions required in the separation without their introduction into the syringe pump. All necessary reagents, including the "cow" or source solution, were placed around valve 200. Valve 304 was used to collect the effluents in separate containers, or to direct them towards disposal. The efficiency of the automated separations was monitored using a portable high purity germanium gamma spectroscopy (HPGe) unit. The product fractions of Bi-213, the fractions of the scrubber, and the solutions of "cow" or of origin of Ac-225, were collected and counted to estimate the recovery and purity of the Bi-213, and the Ac losses. -225 during the separation. The counting experiments were performed using standard procedures. Example 1 An experiment was conducted using the stacked apparatus and method of the present invention, to demonstrate the separation of about 3 milli-curie of Bi-213 from Ac-225. A 25-millimeter anion exchange membrane disc (3M Company) was used, St. Paul MN) as the separation medium in separator 302. Due to the low activity of the radionuclides, low pressure valves were used (evaluation of gas pressure 35 kg / cm2). Table El-1 and Figures 4a, 4b show the results. The eluent fractions were collected in increments of 1 milliliter, in order to evaluate the elution profile of Bi-213. Gamma spectroscopy indicated that the "cow" or source of Ac-225 solution was recovered quantitatively (within the counting errors) in the original storage vessel. A good recovery of the product was achieved using an eluent of 0.1 M sodium acetate. Figure 4a shows that the elution of Bi-213 provides approximately 73 percent of the activity of Bi-213 recovered in the first milliliter of the eluent solution. . Figure 4b shows that more than 87 percent of the Bi-213 product was recovered with 4 milliliters of the sodium acetate eluent.

Table El-1. Results of the automated separation experiment using ion exchange membrane Solution Ac-225 Bi-213 Feeding 3 ml 0.5M HCl 102% 0% Trace Ac-Scrubber 4 ml. of HCl not detected 1.51% 0.005 M Separation 8 mi. of NaOAc not detected 90.3% 0.1 M Membrane not detected 4.36% Product Balance 96.17% Example 2 An experiment was conducted with the apparatus and the stacked method of the present invention, wherein the separator 302 had a miniature anion exchange column, instead of an anion exchange membrane. The valves were as in Example 1. The miniature sorbent column was constructed from FEP tubing with an internal diameter of 1.6 millimeters (Upchurch) using connectors and adaptations without flanges of 1 / 4-28 (Upchurch), and porous glass of FEP of 25 microns (Alltech Associates, Deerfield, IL). The length of the column was 3 centimeters (calculated volume of 0.06 milliliters). The column was packed with strongly basic anion exchange particles based on surface derivatized styrene (particle size 50 microns) in a Cl form obtained from the OnGuard-AMR column (Dionex Corporation, Sunnyvale CA). of an air segment used to separate the aspirated areas was 2 milliliters The reagent volumes and the flow rates for the column separation experiment are listed in Table E2-1. flow for the elution step Eluent fractions were collected in increments of 1 milliliter Separation was performed using 3 milliliters of the cow solution or source containing trace amounts of Ac-225 / Bi-213. Approximately 2 milliliters of the cow solution or source of the test was used (due to a programming error) In order to evaluate the effectiveness of the procedure After separation, the used portion of the source or cow solution was recovered in a separate vessel.

Table E2-1 Separation parameters of the experiment in column Step Reagent Volume Flow Speed Conditioning HCl 0.5 M 2 mi. 1 mi. of the column Load of cow HCl 0.5 M approx. 2 ml 1 ml / min. or trace solution of Ac-of origin 225 / BÍ213 HCl scrubber 0.005 M 0.5 ml 1 ml / min.

Elution of Bi NaOAc 0.1 M 3 ml. 0.5 ml / min. (reverse flow direction) The results of the automated separation of Bi-213 using a miniature ion exchange column are given in Table E2-2. Table E2-2. Results of the automated separation experiments using a 50 microliter ion exchange column. Solution Ac-225 Bi - 213 Feeding 2 ml of HCl 0.5M 101% 0% trace of Ac- Scrubber 0.5 ml. of HCl not detected 1. 5 1% 0.005 M Separation 3 mi. of NaOAc not detected 94% 0.1 M Column not detected 5. 7% Balance of the Product 101. 2% As in the case of a membrane separation, the recovery of Ac-225 of origin or "cow" was quantitative within the counting errors. It got a good • product recovery. The first milliliter of eluent 5 of the product contained approximately 70 percent of the activity of the product. Approximately 94 percent of the Bi-213 product was recovered with 3 milliliters of 0.1M sodium acetate eluent. These preliminary results show that the Bi-213 automated production can be performed • Efficiently using a miniature ion exchange column. The choice of sorbent (non-porous ion exchange pearls, functionalized superficially) provides rapid exchange kinetics.

Furthermore, it was observed that the miniature column is very efficiently flooded with air, which removes any interstitial fluid. This is convenient for recovery of a "cow" or source solution. In addition, the dead volumes of the column reactor were substantially more small in relation to a membrane disc used in a previous experiment. This is desirable for high separation factors. In complementary experiments, we evaluated the operation of a commercially thinned microcolumn available (volume of 0.5 milliliters) packed with On-Guard-A ion exchange beads. The "cow" or source and debugger solutions were loaded at the narrow end, while the elution step was performed from the widest end. The experimental results (recovery of Bi and elution profile) were comparable with those obtained using the non-thinned column. Example 3 Experiments were conducted to demonstrate the automated separation of B? -213 using approximately 16 mCi of Ac-225. The approximately 16 mCi of 225Ac were received from ORNL, as a dry chloride salt in a V-flask, as shown in Table 3.1. The 225Ac was dissolved in 3.1 milliliters of 0.5M HCl and sampled. The 225Ac received was 16.35 mCi. The ratio of 225Ac to 225Ra was 391, compared to the 225Ac product of > 1,068. The ratio of 225Ac to 229Th was determined at 2.54 E + 4. The ICP analysis shows contamination of Al and Cr. This contamination is equal to 0.07 milligrams of Al, and 0.005 milligrams of Cr per mCi of 225Ac. A 25-millimeter anion exchange membrane disk (3M Company, St. Paul MN) was used as the separation medium in separator 302, as in Example 1. However, high-pressure valves were used (evaluation of gas pressure of 350 kg / cm2), due to the increased radionuclide activity compared with examples 1 and 2. The experimental procedure used in this experiment was in sequence, imitating a manual operation. Accordingly, the solutions of "cow" or source of Ac-225 and purification (washing) were not stacked in the pipe segment 102 as in Examples 1 and 2, but rather, the solutions of "cow" or of origin and purifier were aspirated and supplied sequentially. Table E3-1. 225Ac Feeding Analysis ORNL Isotope Activity Ac-225 / isotope ratio At 10:34 12/16/97 Ac-225 16.35 mCi 1 Bi-213 17.2 mCi -1 Ra-225 0.059 mCi 391 Th-229 < 0.64 μCi 2.54 E + 4 Pu239 / 240 < 0.062 mCi > 264 ICP analysis (3 ml feed: 16.35 mCi) At 391 ppm Cr 27 ppm Others < detectable An air segment of 0.25 milliliters was placed in the pipe segment 102 at the beginning of the separation process, and was not expelled until the end of the separation. The volume of the air segment used to separate the zones in the containment coil was 1 milliliter. This segment of air was propelled through the membrane to recover the solutions. Following the supply of solution, an additional volume of air (10 milliliters) was drawn into the coil, and was supplied through the membrane to ensure complete removal of the liquid from the membrane disc and transport lines. The separation begins with the membrane disc and all transport lines filled with air. The membrane disc is placed vertically, with the side of the luer adapter on top. The 3M disc was washed with 0.005 M HCl to remove the interstitial feed and the acid. The anion was then eluted by complexing with 213Bi chlorine sorbed at increments of 1 milliliter / minute, using 0.1 M NaOAc, pH 5.5. The 3M membrane (after elution), the 4 milliliters of wash solution, and each of the 1 milliliter effluent fractions were sampled and counted using the portable GEA system. A sample (10 microliters) of the first milliliter of effluent was sent to the analytical laboratory for full analysis; and the remaining 1 milliliter was used for link studies. The previous test was repeated after approximately 3 hours of growth of 213Bi. The conditions and results are shown in Table E3-2. Table E3-2. Conditions of Elution and Results Conditioning of 0.5 M HCl, at @ 10 ml / min. "cow" or 5Ac source solution: 3 ml Hcl 0.05M -16 mCi 225Ac, @ 4 ml / min. Wash solution: 4 ml of 0.005M HCl, @ 10 ml / min. Elution: 4 ml of 0.1M Na acetate, pH -5.5, ® 1 ml / min.

Results (Table E3-3) for an elution test, using the method and apparatus of the present invention: Table E3-3. Elution Test Results 11 Elution, 1 milliliter% Bi 1 69.8 2 11.9 3 4.0 4 2.1 Membrane 3M 8.6 Wash, 4 ml. 2.5 Material 99.9 Balance The experimental procedure described above was applied to separate Bi-213 from 16 mCi of Ac-225. Approximately 88 percent of 213Bi was recovered in 4 milliliters of 0.1M NaOAc, pH of 5.5, Figures., 5a and 5b. Approximately 80 percent of the recovered Bi-213 was present in the first milliliter of the eluent solution. Example 4 Two experiments were conducted demonstrating the binding of the 213Bi products of Example 3. The two proteins included a canine monoclonal antibody CA 12.10C12, which is reactive with the CD45 antigen on hematopoietic cells and recombinant streptavidin (r-Sav). The r-Sav was humidified with 1.5 CHX-B DTPA chelates / molecule. In each labeling / binding reaction, an amount of 200 micrograms of r-Sav in 120 microliters of phosphate buffered saline (PBS) was used. The canine anti-CD45 monoclonal antibody was modified with 3.6 CHX-B DTPA chelates / molecule. In each reaction, an amount of 100 micrograms of monoclonal antibody was used in 120 microliters of phosphate buffered saline. The 120 microliters of protein solution were mixed with 100 microliters of 1M NaOAc pH of 5, and about 300 microliters of 213Bi from the first fraction of the eluent. An initial determination of the amount of radioactivity was made using a Capintec CRC-7 dose calibrator. After 10 minutes of reaction time, the mixture was placed on the top of a column by exclusion of sizes NAP-10 (G-25), and eluted. Elution fractions (200 microliters of phosphate buffered saline each) were collected in separate microcentrifuge tubes and counted. The empty reaction bottle and the eluted NAP-10 column were also counted. The results of the counting were corrected for the decay for the half-life of 213Bi, and a balance of radioactivity was determined. The results of two tests are shown in Tables 4-1 and 4-1.

Table 4-1. Marking Results Using PNNL, Test # 1 Protein - 120 microliters (200 micrograms of r-Sav) Regulator- 100 microliters of 1M NaOAc, pH of 4 300 microliters of 213Bi containing 2.36 mCi Results: Reading Reading% of Time Capintec: CRC - 7 Initial Initial Correction 11:50 256 256 1-1 12:21 0 .2 0.3 0.1 1-2 12:22 0 .0 0 0 1-3 12:23 0. 2 0.3 0.3 1-4 12:25 0, .5 0.83 0.3 1-5 12:27 8. .3 14.2 5.5 1-6 12: 30 32. .3 56.7 22.1 1-7 12:32 46, .2 84 32.8 1-8 12:34 32, .3 61 23.8 1-9 12:35 13, .8 26.3 10.3 Column 12:39 4., 0 8.2 3.2 251.7A 1-7 Re-execution 12:37 43. .3 84.3 Balance A Activity of 98.3% Table 4-2 Marking Results Using PNNL Test # 2 Protein - 120 microliters (100 micrograms of canine mAb Anti-CD45) Regulator - 100 microliters of 1M NaOAc pH of 4 200 microliters, containing 1.9 mCi of 213Bi Results: Reading Time Corrected Reading % of initial Initial 2:06 207 207 2-1 2:34 0.2 0.3 0.15 2-2 2:35 0.1 0.15 0 2-3 2:36 0.1 0.15 0 2-4 2: 37 0.1 0.17 0.08 2-5 2:37 6.1 9.5 4.7 2-6 2:38 24.6 39.0 19.3 2-7 2: 39 33.0 52.8 26.2 2-8 2:39 22.2 35.5 17.6 2-9 2:40 7.4 12.0 6.0 2-10 2:40 2.4 3.9 1.9 2-11 2 : 41 1.7 2.8 1.4 Column 2:31 20.9 30.0 14.8 Flask 2: 41 9.4 15.4 7.6 201.7 Activity Balance of 99.7% After purification on NAP-10 columns, 72 percent (1.7 mCi) of 213Bi was labeled with r-Sav, and 69 percent (1.31 mCi) was labeled with canine anti-CD45 mAb, 12.10C12. These percentages are derived from the data in Tables 4-1 and 4-2 and are sufficient for therapeutic use.

CLOSURE Although a preferred embodiment of the present invention has been shown and described, it will be apparent to those skilled in the art that many changes and modifications can be made without departing from the invention in its broader aspects. Accordingly, it is intended that the appended claims cover all changes and modifications that fall within the true spirit and scope of the invention.

Claims (22)

1. NOVELTY OF THE INVENTION Having described the foregoing invention, it is considered as a novelty, and therefore, the content of the following is claimed as property: CLAIMS 1. A method for separating a short-lived child isotope from an isotope long-life parent, which comprises the steps of: (a) filling a connected bidirectional pump, and a segment of tubing connected thereto, with a regulating liquid; (b) placing a volume of a gas in contact with the regulating liquid, removing a first quantity of the regulating liquid; (c) directing a first sample of liquid from a mixture of the short-lived child isotope and the long-lived progenitor isotope in the pipe segment, removing a second quantity of regulating liquid, where the first liquid sample is separated from the regulating liquid by the volume of the gas; (d) passing the first liquid sample through a separator to obtain the short-lived isotope son. The method according to claim 1, further comprising directing a second liquid into the pipe segment, either by a stacking method or a sequential method. 3. The method according to claim 2, characterized in that the stacking method comprises the steps of: conditioning the separator, loading the debugger, loading the cow or source solution, supplying the cow or source solution to through the separator, and elution or collection of the child. 4. The method according to claim 3, characterized in that the conditioning of the separator comprises the steps: 2a.1. direct a gas into the pipe segment, through a first multi-position valve; 2a.2. directing a separating conditioner reagent into the pipe segment, through a reagent gate, into the first multi-position valve; 2a.3 eject the conditioning reagent from the separator from the pipe segment, through the first multi-position valve, through the separator to a waste gate in a second multi-position valve, and expel the gas behind the conditioning reagent from the separator; 2a.4. switching the first multi-position valve to a waste gate position, and expelling the remaining gas from the pipe segment to a waste gate in the first multi-position valve, followed by the expulsion of a carrier solution; and 2a.5. fill the separator and the transport lines with the gas. 5. The method according to claim 4, characterized in that the debugger load comprises the steps of: 3a.5. place the second multi-position valve in a cow gate position or source solution; 3a.6. placing the first multi-position valve in a gate position of the separator; 3a.8. Supply a cow or source and air solution to the separator, where the short-lived isotope is retained inside the separator for subsequent elution, or for the son's collection, and direct the effluent to a storage container or storage tank. cow, through the second multi-position valve; 3a.9. placing the first and second multi-position valves in a debug gate position; 3a.10. supplying a purifying solution and air through the separator to a scrubber gate, in the second multi-position valve; and 3a.11. switch the first multi-position valve to the waste gate position, and expel the remaining air from the pipe segment to the waste gate on the first multi-position valve, followed by a carrier solution. 6. The method according to claim 5, characterized in that the elution comprises the steps of: 4a.1. reverse the flow direction through the separator; 4a.2. place the second multi-position valve in a product gate position; 4a.3. directing an air segment into the pipe segment through the first multi-position valve; 4a.4. directing an eluent into the pipe segment through the first multi-position valve; 4a.5. eject the eluent from the pipe segment through the first multi-position valve, through the separator, where the short-lived isotope is eluted from the separator, and through the second multi-position valve, to a container of product; 4a.6. Dose air through the pipe segment after the eluent; and 4a.7. switching the first multi-position valve to the waste gate position, and expelling the remaining air from the pipe segment to the waste gate on the first multi-position valve, followed by flooding with a carrier solution. The method according to claim 2, characterized in that the sequential method comprises the steps of: initializing, conditioning the separator, loading and supplying the solutions of cow or origin and debugger, and eluting an isotope son of life cuts from a long-lived progenitor isotope. 8. The method according to claim 7, characterized in that the initialization comprises the steps of: 1.1. establish the first multi-position valve in a waste gate position, and empty a syringe; and 1.2. sucking an air segment into the pipe segment. The method according to claim 2, characterized in that the method in sequence comprises the steps of: conditioning the separator, loading and supplying the cow or source solutions and debugger, and eluting an isotope short-lived son . 10. The method according to claim 9, characterized in that the conditioning of the separator comprises the steps of: 2b.1. directing a gas into the pipe segment through a first multi-position valve; 2b.2. aspirating a separating conditioner reagent through the first multi-position valve into the pipe segment; 2b.3. expelling the conditioning reagent from the separator from the pipe segment through the separator, followed by expelling the air; 2b.4. sucking the air through the first multi-position valve into the pipe segment; and 2b.5. switch the first multi-position valve to a separator gate position, and expel the air through the separator. 11. The method according to claim 9, characterized in that the loading and delivery of the cow or origin solution comprises the steps of: 3b.1. sucking the air through a first multi-position valve into the pipe segment; 3b.2 to switch the first multi-position valve to a cow gate position or source solution, and to direct a cow or source solution into the pipe segment; 3b.4. switching the first multi-position valve to a separator gate position, and switching a second multi-position valve to a cow return or source solution gate position; 3b.5. ejecting the cow or source solution from the pipe segment through the separator, to a cow storage tank or source solution; 3b.6. switching the first multi-position valve to an air gate position, and drawing air into the pipe segment; 3b.7. switch the first multi-position valve to the separator gate position; and 3b.8. Expel the air from the pipe segment to the cow storage tank or source solution. 12. The method according to claim 11, characterized in that the charge and supply of treatment solution comprises the steps of: 3b.9. switch the first multi-position valve to the position of the air damper, and switch the second multi-position valve to the position of the scrubber damper; 3b.10. sucking air into the pipe segment through the first multi-position valve; 3b.11. switching the first multi-position valve to a position of the scrubber gate, and directing a scrubbing solution into the pipe segment; 3b.12. switching the first multi-position valve to the separator gate position, ejecting the treatment solution from the pipe segment through the separator to a scrubber gate in the second multi-position valve; 3b.13. switch the first multi-position valve to the air gate position, and draw the air into the pipe segment; and 3b.14. switching the first multi-position valve to the separator gate position, and expelling the air from the pipe segment, through the separator, to a waste gate in the second multi-position valve. 13. The method according to claim 12, characterized in that the elution of a short-lived child isotope comprises the steps of: 4b.1. switching the first multi-position valve to the air gate position, and switching the second multi-position valve to the product gate position; 4b.2. sucking air into the pipe segment through the first multi-position valve; 4b.3. switching the first multi-position valve to an eluent gate position, and directing an eluent solution into the pipe segment; 4b.5. switching the first multi-position valve to the separator gate position, and expelling the eluent solution from the pipe segment through the separator, to a product container, through the second multi-position valve; 4b.6. switch the first multi-position valve to the air gate position, and draw the air into the pipe segment; and 4b.7. switch the first multi-position valve to the separator gate position, and expel the air from the pipe segment to the product container. The method according to claim 1, characterized in that the short-lived child isotope comprises Bi-213, and the long-lived parent isotope comprises Ac-225. 15. The method according to claim 1, characterized in that the separator is selected from the group consisting of an anion exchange column and an anion exchange membrane. 16. An apparatus for separating a short-lived child isotope from a long-lived parent isotope, which comprises: (a) a bidirectional pump connected to a pipe segment, this bidirectional pump and the pipe segment being filled with a regulating liquid; (b) a first valve connected to the pipe segment, and connected to a gas supply for directing a volume of a gas between the regulating liquid and the first liquid sample; and (c) a second valve connected to the pipe segment, which makes it possible to direct a first liquid sample of a mixture of the short-lived child isotope and the long-lived parent isotope into the pipe segment, by withdrawing a quantity of the regulating liquid; whereby, (d) the first liquid sample is prevented from contacting the regulating liquid by the volume of the gas therebetween. The apparatus according to claim 16, characterized in that the first and second valves are on a first multi-position valve. 18. The apparatus according to claim 16, characterized in that the first and second valves are operated by a microprocessor. 19. The apparatus according to claim 17, characterized in that it also comprises a separator connected to a separation gate of the first multi-position valve. 20. The apparatus according to claim claimed in claim 19, characterized in that the separator is selected from the group consisting of an anion exchange membrane, anion exchange column, and combinations thereof. The apparatus according to claim 19, characterized in that it also comprises a second multi-position valve connected to an outlet of the separator. 22. The apparatus according to claim 17, further comprising a two-position valve connected to the first multi-position valve, a separator connected to the two-position valve, and a second multi-position valve connected. to the two-position valve. SUMMARY The present invention is a method for separating a short-lived child isotope from a longer-lived parent isotope with the recovery of the parent isotope for further use. Using a system with a bidirectional pump and one or more valves, a solution of the parent isotope is processed to generate two separate solutions, one of which contains the isotope son, from which the parent has been removed with a high decontamination factor, and the other solution contains the recovered parent isotope. The process can be repeated on this solution of the parent isotope. The system with the fluid impulse and one or more valves, is controlled by a program in a microprocessor that executes a series of steps to perform the operation. In one approach, the source solution is passed through a separation means that selectively retains the desired child isotope, while the parent isotope and the matrix pass through the medium. After washing this medium, the isotope son of the separation medium is released using another solution. With the automated generator of the present invention, all solution handling steps necessary to perform a daughter / parent radionuclide separation, for example BI-213 from the Ac-225 origin solution, are performed in a consistent, enclosed format, and remotely operated. The exposure of the operator and the extent of contamination are minimized in a large proportion compared to the manual generator method described in United States Patent Application Number 08 / 789,973 incorporated herein by reference. Using (16) mCi of Ac-225, there was no detectable external contamination of the instrument components. The most representative figure of the invention is number 3A. * * * * *