SYSTEM FOR AUTOMATICALLY PRODUCING RADIOISOTOPES

TECHNICAL FIELD The present invention relates to a system for automatically producing radioisotopes. BACKGROUND ART

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 (WO9707122) . 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 . DISCLOSURE OF INVENTION

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, characterized by comprising a target carrier; an electrodeposition unit for electrodepositing a target in said target carrier; an irradiation unit for irradiating said target in said target carrier; first transfer means for transferring the target carrier from the electrodeposition unit to the irradiation unit; an electrodissolution unit for electrodissolving the

irradiated target without corroding said target carrier (8) ; second transfer means for transferring the target carrier from the irradiation unit to the electrodissolution unit; a purifying unit for purifying the radioisotope of the non-reacting target and impurities; third transfer means for transferring the electrodissolved irradiated target from the electrodissolution unit to the purifying unit; and a central control unit for controlling the operating units and transfer means to automate the entire process.

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.

BRIEF DESCRIPTION OF THE DRAWINGS 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 2a shows a section of the target carrier

according to another embodiment;

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 4a shows a section of the electrolysis unit according to another embodiment;

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. BEST MODE FOR CARRYING OUT THE INVENTION

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 2a, according to a preferred embodiment, a hole 11a is made in the partition wall 11 to allow a more effective cooling of the coating 12a.

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. As shown in figure 4a, according to a preferred embodiment, electrolytic cell 19 comprises a platinum electrode 23a connected with a platinum tube 24a, in which an electrolytic solution comprising the metal to be deposited is fed. In other words, in this embodiment the platinum tubee 24a works as a delivery tube and the tubes 21 e 22 are used to remove the electrolytic solution or to clean the electrolytic cell 19. In the preferred embodiment shown in figure 4a the four springs 26 and the disk body 27 are absent, and other means (not shown) are used 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 HNO ₃ 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 or by the platinum pipe 24a. 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 re- dissolved 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 ⁶⁰ Cu, ⁶¹ Cu, ⁶⁴ Cu - A solution of 10 ml of ( ⁶⁰ Ni, ⁶¹ Ni, ⁶⁴ Ni) 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 5O ⁰ 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 2OmA. 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 6O ⁰ 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 cm ² 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 5O ⁰ 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 ( ⁶⁰ Cu, ⁶¹ Cu, ⁶⁴ Cu) is transferred automatically to purifying unit 4, where the manufactured

radioisotope ( ⁶⁰ Cu, ⁶¹ Cu, ⁶⁴ Cu) is separated from the respective starting nickel isotope and any other radioactive and metal impurities .

- Preparation of radioisotope ¹¹⁰ In - 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 3O ⁰ 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 6O ⁰ 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-llO/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.