Note: Descriptions are shown in the official language in which they were submitted.
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
1
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 non-
radioactive 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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
2
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.
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
3
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
4
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)
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
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
5 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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
6
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
of conduit 18.
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
7
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
8
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
9
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
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
5 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
10 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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
11
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
12
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
CA 02606643 2007-10-29
WO 2006/114433 PCT/EP2006/061853
13
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.
