EP1717819B1

EP1717819B1 - System for automatically producing radioisotopes

Info

Publication number: EP1717819B1
Application number: EP05425262A
Authority: EP
Inventors: Paolo Bedeschi
Original assignee: Comecer SpA
Current assignee: Comecer SpA
Priority date: 2005-04-27
Filing date: 2005-04-27
Publication date: 2011-07-20
Anticipated expiration: 2025-04-27
Also published as: WO2006114433A2; WO2006114433A3; EP1717819A1; ES2369482T3; CA2606643C; DK1717819T3; CA2606643A1; ATE517418T1; US20100025251A1

Abstract

A system (1) for automatically producing radioisotopes, and including a target carrier (8); an electrodeposition unit (2) for electrodepositing a target in the target carrier; an irradiation unit (3) for irradiating the target in the target carrier (8); first transfer means (5, 18) for transferring the target carrier from the electrodeposition unit (2) to the irradiation unit (3); an electrodissolution unit (2) for electrodissolving the irradiated target; second transfer means (5, 18) for transferring the target carrier from the irradiation unit (3) to the electrodissolution unit (2); a purifying unit (4) for purifying the radioisotope of the non-reacting target and impurities; third transfer means (6, 22) for transferring the electrodissolved irradiated target from the electrodissolution unit (2) to the purifying unit (4); and a central control unit (7) for controlling the operating units and transfer means to automate the entire process.

Description

The present invention relates to a system for automatically producing radioisotopes.
Radioisotopes have long been produced by cyclotron irradiation for medium- or low-energy (5-30 MeV) medical applications. Radioisotopes have many important industrial and scientific uses, the most important of which is as tracers : by reactions with appropriate nonradioactive precursors, radiodrugs are synthesized and, when administered in the human body, permit diagnosis and therapy monitoring by Positron Emission Tomography (PET), especially in the treatment of tumours. By measuring radiation, it is also possible to follow all the transformations of the element and/or related molecule in chemistry (reaction mechanism research), biology (metabolism genetics research), and, as stated, in medicine for diagnostic and therapeutic purposes.
The only automated passage in known systems for producing radioisotopes is that between the irradiation station and the purifying station, where the desired radioisotope is separated not only from the target carrier material but also from the non-reacting target and any impurities ( W09707122 ).
Moreover, in known production systems, once the target has been irradiated, the target carrier, on which the starting metal isotope is deposited, is dissolved together with the target and subsequently removed from the manufactured radioisotope by means of a purification process.
Such a solution obviously calls for more complex, prolonged purification than that required to simply separate the manufactured radioisotope from the starting isotope.
It is an object of the present invention to provide a system for automatically producing radioisotopes, and which provides for more efficient production, in terms of output, as compared with known systems.
According to the present invention, there is provided a system for automatically producing radioisotopes as in claim 1.
In a preferred embodiment, the electrodeposition unit and the electrodissolution unit comprise the same electrolytic cell, and the first transfer means and second transfer means coincide.
In a further preferred embodiment, the first transfer means and second transfer means comprise a conduit connected to a pneumatic system and housing said target carrier in sliding manner.
A non-limiting embodiment of the invention will be described by way of example with reference to the accompanying drawings, in which:

Figure 1 shows an overall view of a preferred embodiment of the system for automatically producing radioisotopes according to the present invention;
Figure 2 shows a section of the target carrier used in the system according to the present invention;
Figure 3 shows a view in perspective of a supporting structure of the electrolysis unit of the Figure 1 system;
Figure 4 shows a section of the electrolysis unit of the Figure 1 system;
Figure 5 shows a view in perspective of the irradiation unit of the Figure 1 system;
Figure 6 shows a section of a detail of the Figure 5 irradiation unit;
Figure 7 shows a front view of the purifying unit of the Figure 1 system.

Number 1 in Figure 1 indicates as a whole the system for automatically producing radioisotopes according to the present invention.
System 1 comprises an electrolysis unit 2 for both electrodeposition and electrodissolution; an irradiation unit 3 fixed directly to a cyclotron C; a purifying unit 4; transfer means 5 for transferring the target between electrolysis unit 2 and irradiation unit 3; transfer means 6 for transferring the dissolved target from electrolysis unit 2 to purifying unit 4; and a central control unit 7 for fully controlling operation of system 1.
System 1 comprises a target carrier 8 (Figure 2) defined by a cylindrical wall 9 having a truncated-cone-shaped end portion 10, and by a partition wall 11 inside and perpendicular to cylindrical wall 9. Partition wall 11 and cylindrical wall 9 define two separate cylindrical cavities 12 and 13. More specifically, cylindrical wall 9 thickens inwards at cavity 12; cylindrical wall 9 and partition wall 11 are made of aluminium or stainless steel; and cylindrical cavity 12 is lined with a coating 12a of platinum or niobium or iridium.
As shown in Figure 3, electrolysis unit 2 is supported on a supporting structure 14, which comprises a gripping head 15; four supporting members 16 on which to store four target carriers 8; and a terminal 17 for connecting a conduit 18, as described below. Gripping head 15 is connected to a vacuum pump by a fitting 15a, and is moved vertically by a pneumatic cylinder and horizontally by a screw-nut screw system connected to a toothed belt. Each supporting member 16 has a target carrier presence sensor.
Electrolysis unit 2 comprises an electrolytic cell 19; and a heater 20 housed, in use, inside cylindrical cavity 13 of target carrier 8.
As shown in Figure 4, electrolytic cell 19 comprises a delivery tube 21; a return tube 22 defining the dissolved target transfer means 6; a platinum electrode 23 with a corresponding platinum wire 24; a gold or platinum disk electrode 25; and four springs 26 wound about respective assembly screws, and which act on a disk body 27 for disconnecting target carrier 8.
Heater 20 comprises an electric resistor 28, and a temperature probe 29.
As shown in Figures 3 and 5, transfer means 5 for transferring target carrier 8 comprise a conduit 18 connected to a known pneumatic system (not shown for the sake of simplicity) by which the target carrier is pushed or drawn along conduit 18.
As shown in Figure 5, irradiation unit 3 comprises a grip pin 31 housed in use inside cylindrical cavity 13 of target carrier 8; a rotary actuator 32 connected to grip pin 31; a linear actuator 33 also connected to grip pin 31; and a pneumatic cylinder 34 connected to a terminal 35 of conduit 18.
As shown in Figure 6, inside grip pin 31 are formed a central cooling water feed conduit 36 connected to a fitting 37; an intermediate annular cooling water return conduit 38 connected to a fitting 39; and an outer annular conduit 40 connected to a vacuum pump by a fitting 41.
As shown in Figure 7, purification unit 4 comprises an ionic purification column 42, two pumps 43, a reactor 44, and a network of valves and vessels, and is electronically controlled to supply electrolytic cell 19 with the appropriate electrolytic solution containing the isotopes of the metals to be electrodeposited inside cavity 12 of target carrier 8, to supply electrolytic cell 19 with an HNO₃ solution for electrodissolving the irradiated target, to separate the radioisotope from the starting isotope and other radioactive impurities by ion chromatography, and to supply solvents for cleaning electrolytic cell 19, the transfer lines, and the components used to separate the radioisotope.
In actual use, a target carrier 8 is picked up by gripping head 15 and placed on heater 20, so that heater 20 is housed inside cylindrical cavity 13 of target carrier 8; and electrolytic cell 19 is then lowered into the Figure 4 position, i.e. in which disk electrode 25 contacts an edge portion of coating 12a of cylindrical cavity 12 of target carrier 8. In the Figure 4 condition, an electrolytic solution, from purifying unit 4 and in which the isotope of the metal to be deposited is dissolved, is fed in by delivery tube 21. As the solution flows in, the difference in potential is applied to the electrodes, and the isotope for irradiation is deposited. Once deposition is completed, the electrolytic solution is removed, and electrolytic cell 19 and cylindrical cavity 12 are cleaned using deionized water and ethyl alcohol in succession, which are then removed by a stream of helium. Once the cleaning solvents are removed, target carrier 8 is heated and maintained in a stream of gas to dry the deposited metal.
At this point, electrolytic cell 19 is raised, and gripping head 15 removes target carrier 8 and places it either on a supporting member 16, pending irradiation, or directly inside terminal 17, from which it is blown inside conduit 18 by a stream of compressed air. Target carrier 8 is fed along conduit 18 to terminal 35 of irradiation unit 3, where the presence of carrier 8 is detected by a sensor.
On reaching terminal 35, target carrier 8 is retained by grip pin 31 by virtue of the vacuum produced in outer annular conduit 40. Pneumatic cylinder 34 then lowers terminal 35 and conduit 18, and rotary actuator 32 and linear actuator 33 move grip pin 31 and target carrier 8 into the irradiation position. More specifically, carrier 8 is successively rotated 90° and translated to position cylindrical cavity 12 facing an irradiation opening 45 shown in Figure 5. Once irradiated, target carrier 8 is replaced inside terminal 35 by linear actuator 33, rotary actuator 32, and pneumatic cylinder 34; at which point, the vacuum holding target carrier 8 on grip pin 31 is cut off, and the vacuum pump connected to conduit 18 is activated to return target carrier 8 to terminal 17.
On reaching terminal 17, the target carrier is picked up by gripping head 15 and placed back on heater 20 as described previously; at which point, electrolytic cell 19 is lowered so that disk electrode 25 contacts the edge portion of coating 12a of cylindrical cavity 12 of target carrier 8. This time, however, unlike the electrodeposition operation described above, a portion of the coating of cylindrical cavity 12 is preferably left exposed to employ its catalyst properties for the electrodissolution reaction. Once the above situation is established, an acid solution, from purifying unit 4 and comprising nitric or hydrochloric acid, is fed in by delivery tube 21, and target carrier 8 is appropriately heated by resistor 28.
At this point, electrodissolution is performed, by inverting one polarity of the electrodes with respect to electrodeposition, and the resulting solution is sent by a stream of inert gas to purifying unit 4.
Once the acid solution is removed from the electrolytic cell, the electrolysis unit is cleaned and dried using deionized water and ethyl alcohol, after which, gripping head 15 can pick up another target carrier 8 and commence another work cycle.
The acid solution from the electrodissolution operation, and therefore containing the starting metal isotope and the radioisotope obtained by irradiation, is transferred to reactor 44 where the nitric acid is evaporated. The isotope/radioisotope mixture is redissolved in a hydrochloric acid solution, radioactivity is measured, and the solution is transferred in a stream of helium to ionic purification column 42. The starting metal isotope is recovered and used for further deposition.
The preparation of two radioisotopes will now be described in more detail by way of example.

- Preparation of radioisotope ⁶⁰Cu, ⁶¹Cu, ⁶⁴Cu -

A solution of 10 ml of (⁶⁰Ni, ⁶¹Ni, ⁶⁴Ni) comprising nickel sulphate and boric acid is fed into a vessel in purifying unit 4. Once target carrier 8 and electrolytic cell 19 are set up as shown in Figure 4, the nickel-containing acid solution is circulated, at a temperature of 25° to 50°C, inside cylindrical cavity 12 of target carrier 8 by a closed-circuit system supplied by one of pumps 43. When the desired temperature is reached, the voltage control is activated automatically and turns on the voltage and current supply pre-set to 3V and 20mA. The electrodeposition operation lasts an average of 24h, after which, the system is arrested and, once the electrolytic solution circuit is emptied, electrolytic cell 19 and cavity 12 are cleaned using deionized water and ethyl alcohol in succession. Once the cleaning solvents are eliminated, target carrier 8 is heated to 60°C and maintained in a stream of gas for at least 15 minutes to dry the surface of the nickel deposit. The average yield of metal nickel on the bottom of cylindrical cavity 12 corresponds to 50±2% of the initially dissolved nickel. When the above operations are completed, target carrier 8 is transferred automatically along conduit 18 to the irradiation unit, and, after irradiation, is transferred automatically back to electrolysis unit 2.
Once target carrier 8 and electrolytic cell 19 are set up as shown in Figure 4, electrolytic cell 19, while ensuring disk electrode 25 remains contacting the edge portion of coating 12a, is raised roughly 0.2 mm corresponding to an 88 cm² free-platinum surface formed on the lateral wall of cylindrical cavity 12. The free-platinum surface acts as a catalyst in dissolving the nickel, which is done using a 5 ml solution of nitric acid 4M contained in a vessel in purifying unit 4. The acid solution is circulated for about 10-20 minutes, at a flow rate of 0.5-2 ml/min, inside cylindrical cavity 12 of target carrier 8 heated to a temperature of 25 to 50°C; in which conditions, dissolution of the target is quantitative. Once dissolution is completed, the acid solution containing the dissolved nickel and the manufactured radioisotope (⁶⁰Cu, ⁶¹Cu, ⁶⁴Cu) is transferred automatically to purifying unit 4, where the manufactured radioisotope (⁶⁰Cu, ⁶¹Cu, ⁶⁴Cu) is separated from the respective starting nickel isotope and any other radioactive and metal impurities.

- Preparation of radioisotope ¹¹⁰In -

A 10 ml solution of cadmium-110 comprising cadmium fluoborate and ammonium fluoborate is fed into a vessel in purifying unit 4 and to electrodeposition unit 2, where target carrier 8 and electrolytic cell 19 are set up as shown in Figure 4. The acid solution is circulated, at a temperature of 30°C and a flow rate of 0.5-2 ml/min, inside cylindrical cavity 12 by a closed-circuit system fed by one of pumps 43; and, in these conditions, 0.02 A current and 3V voltage are applied for about 4-6h to deposit at least 40mg of cadmium-110. When electrodeposition is completed, the system is cleaned with deionized water and ethyl alcohol, and, once the cleaning solvents are removed, target carrier 8 is heated to 60°C and maintained in a stream of gas for at least 15 minutes to dry the surface of the cadmium-110 deposit.
When the above operations are completed, target carrier 8 is transferred automatically along conduit 18 to the irradiation unit, and, after irradiation, is transferred automatically back to electrolysis unit 2.
Electrodissolution is performed using a 4 ml solution of nitric acid 4M contained in a vessel in purifying unit 4. The acid solution is circulated for about 2 minutes at a flow rate of 0.5-2 ml/min inside cylindrical cavity 12 of target carrier 8 maintained at ambient temperature; in which conditions, dissolution is quantitative. When dissolution is completed, the acid solution containing cadmium-110/indium-110 is transferred automatically to purifying unit 4, where the indium-110 is separated by ionic purification from the cadmium-110 and any other radioactive and metal impurities.
The system according to the present invention has the advantage of preparing radioisotopes automatically and so ensuring high output levels.
Moreover, by providing for electrodissolution of the irradiated metal, the system according to the present invention avoids dissolution of the target carrier, with obvious advantages at the purification stage.

Claims

A system (1) for automatically producing radioisotopes comprising a target carrier (8) an electrodeposition unit (2) for electrodepositing a target in said target carrier; an irradiation unit (3) for irradiating said target in said target carrier (8) ; first transfer means (5, 18) for transferring the target carrier from the electrodeposition unit (2) to the irradiation unit (3); a purifying unit (4) for purifying the radioisotope of the non-reacting target and impurities; and a central control unit (7) for controlling the operating units and transfer means to automate the entire process; said system being characterized by comprising an electrodissolution unit (2) able to electrodissolve said target while avoiding dissolution of the target carrier (8); second transfer means (5, 18) for transferring the target carrier from the irradiation unit (3) to the electrodissolution unit (2); third transfer means (6, 22) for transferring the electrodissolved irradiated target from the electrodissolution unit (2) to the purifying unit (4);
A system as claimed in Claim 1, characterized in that the electrodeposition unit and the electrodissolution unit comprise the same electrolytic cell (2); and in that said first transfer means (5, 18) and said second transfer means (5, 18) coincide.
A system as claimed in Claim 2, characterized in that said first transfer means (5) and said second transfer means (5) comprise a conduit (18) connected to a pneumatic system and housing said target carrier (8) in sliding manner.
A system as claimed in any one of the foregoing Claims, characterized in that said target carrier (8) comprises a cylindrical wall (9), and a partition wall (11) inside and perpendicular to the cylindrical wall (9) to define a first (12) and a second (13) cylindrical cavity separate from each other; said first cylindrical cavity (12) housing the target for irradiation.
A system as claimed in Claim 4, characterized in that said cylindrical wall (9) and said partition wall (11) are made of aluminium or stainless steel; and in that said first cylindrical cavity (12) is lined with a coating (12a) of platinum or niobium or iridium.
A system as claimed in Claim 5, characterized in that said electrolysis unit comprises an electrolytic cell (19); and a heater (20) which is housed in said second cylindrical cavity (13) of the target carrier (8).
A system as claimed in Claim 6, characterized in that said electrolytic cell (19) comprises a platinum electrode (23); and a disk electrode (25) made of gold or platinum and which, in use, contacts an edge portion of the coating (12a) of the first cylindrical cavity (12) of the target carrier (8).
A system as claimed in any one of the foregoing Claims, characterized in that said electrolysis unit (2) is fitted to a supporting structure (14) comprising a pneumatic gripping head (15), and a number of supporting members (16) on which an equal number of target carriers (8) can be stored.
A system as claimed in any one of the foregoing Claims, characterized in that said irradiation unit (3) comprises a grip pin (31); a rotary.actuator (32) connected to the grip pin (31); and a linear actuator (33) also connected to the grip pin (31).
A method of producing radioisotopes comprising a first step of electrodepositing a metal isotope for irradiation inside a target carrier (8) lined with platinum or iridium or niobium; a second step of irradiating the deposited metal isotope; and a fourth step of purifying the radioisotope of the starting metal isotope and any other radioactive and metal impurities; said method being characterized by comprising before said fourth step, a third step of electrodissolving the irradiated metal isotope and the formed radioisotope while avoiding dissolution of the target carrier (8).
A method as claimed in Claim 10, characterized in that said third step comprises the participation of a platinum portion free of surface deposits.
A method as claimed in Claim 11, characterized in that said platinum portion is part of the lining of said target carrier (8).
A method as claimed in any one of Claims 10 to 12, characterized in that said metal isotope is included in the group comprising ⁶⁰Ni, ⁶¹Ni, ⁶⁴Ni and ¹¹⁰Cd.