U.S. patent application number 15/581544 was filed with the patent office on 2017-09-21 for processes, systems, and apparatus for cyclotron production of technetium-99m.
The applicant listed for this patent is TRIUMF. Invention is credited to Francois BENARD, Kenneth R. BUCKLEY, Maurice G. DODD, Victoire HANEMAAYER, Julius Alexander KLUG, Michael S. KOVACS, Cornelia Hoehr MANUELA, Thomas J. MORLEY, Thomas J. RUTH, Paul SCHAFFER, John VALLIANT, Stefan K. ZEISLER.
Application Number | 20170271036 15/581544 |
Document ID | / |
Family ID | 49482067 |
Filed Date | 2017-09-21 |
United States Patent
Application |
20170271036 |
Kind Code |
A1 |
SCHAFFER; Paul ; et
al. |
September 21, 2017 |
PROCESSES, SYSTEMS, AND APPARATUS FOR CYCLOTRON PRODUCTION OF
TECHNETIUM-99M
Abstract
A system for producing technetium-99m from molybdate-100. The
system comprises: a target capsule apparatus for housing a
Mo-100-coated target plate; a target capsule pickup apparatus for
engaging and delivering the target cell apparatus into a target
station apparatus; a target station apparatus for receiving and
mounting therein the target capsule apparatus. The target station
apparatus is engaged with a cyclotron for irradiating the
Mo-100-coated target plate with protons. The irradiated target
capsule apparatus is transferred to a receiving cell apparatus
comprising a dissolution/purification module for receiving therein
a proton-irradiated Mo-100-coated target plate. A conveyance
conduit infrastructure interconnects: (i) the target capsule pickup
apparatus with the target station apparatus, (ii) the target
station apparatus and the receiving cell apparatus; and (iii) the
receiving cell apparatus and the dissolution/purification
module.
Inventors: |
SCHAFFER; Paul; (Richmond,
CA) ; BENARD; Francois; (West Vancouver, CA) ;
BUCKLEY; Kenneth R.; (Vancouver, CA) ; HANEMAAYER;
Victoire; (Richmond, CA) ; MANUELA; Cornelia
Hoehr; (Vancouver, CA) ; KLUG; Julius Alexander;
(Vancouver, CA) ; KOVACS; Michael S.; (London,
CA) ; MORLEY; Thomas J.; (New Haven, CT) ;
RUTH; Thomas J.; (Vancouver, CA) ; VALLIANT;
John; (Ancaster, CA) ; ZEISLER; Stefan K.;
(Vancouver, CA) ; DODD; Maurice G.; (Vancouver,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
TRIUMF |
Vancouver |
|
CA |
|
|
Family ID: |
49482067 |
Appl. No.: |
15/581544 |
Filed: |
April 28, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13870830 |
Apr 25, 2013 |
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15581544 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B22F 1/0088 20130101;
Y02E 30/30 20130101; B22F 7/02 20130101; G21G 1/001 20130101; G21G
2001/0042 20130101; B22F 2999/00 20130101; G21F 5/14 20130101; C25D
13/22 20130101; H05H 6/00 20130101; C25D 13/02 20130101; B22F
2998/10 20130101; G21G 1/10 20130101; B22F 2999/00 20130101; B22F
1/0088 20130101; B22F 9/22 20130101; B22F 2999/00 20130101; B22F
9/22 20130101; B22F 2201/013 20130101; B22F 2998/10 20130101; B22F
1/0088 20130101; B22F 3/10 20130101 |
International
Class: |
G21G 1/00 20060101
G21G001/00; H05H 6/00 20060101 H05H006/00; C25D 13/22 20060101
C25D013/22; C25D 13/02 20060101 C25D013/02; G21G 1/10 20060101
G21G001/10 |
Claims
1. A system for producing technetium-99m from molybdate-100,
comprising: a target capsule apparatus for housing therein a
Mo-100-coated target plate; a target capsule pickup apparatus for
engaging the target capsule apparatus and delivering the target
cell apparatus into a target station apparatus; a target station
apparatus for receiving and mounting therein the target capsule
apparatus, said target station apparatus engaged with a cyclotron
and communicable with said cyclotron for irradiating the
Mo-100-coated target plate with protons; a receiving cell apparatus
for receiving and mounting therein the irradiated target capsule
apparatus; a transfer tube interconnecting the receiving cell
apparatus and the target station apparatus; a
dissolution/purification module for receiving therein a
proton-irradiated Mo-100-coated target plate; a conveyance conduit
infrastructure interconnecting: (i) the target capsule pickup
apparatus with the target station apparatus, (ii) the target
station apparatus and the receiving cell apparatus; and (iii) the
receiving cell apparatus and the dissolution/purification module;
and a supply of oxygen-free atmosphere to the target station
apparatus.
2. The system of claim 1, additionally comprising a booster station
apparatus engaged with the transfer tube.
3. A target capsule apparatus according to claim 1.
4. A target capsule pickup apparatus according to claim 1.
5. A target station apparatus according to claim 1.
6. A target station receiving cell apparatus according to claim
1.
7. A dissolution/purification module according to claim 1.
8. A booster station apparatus according to claim 2.
Description
TECHNICAL FIELD
[0001] The present disclosure pertains to processes, systems, and
apparatus, for production of technetium-99m. More particularly, the
present pertains to production of technetium-99m from
molybdenum-100 using accelerators such as cyclotrons.
BACKGROUND
[0002] Technetium-99m, referred to hereinafter as Tc-99m, is one of
the most widely used radioactive tracers in nuclear medicine
diagnostic procedures. Tc-99m emits readily detectable 140 keV
gamma rays and has a half-life of only about six hours, thereby
limiting patients' exposure to radioactivity. Depending on the type
of nuclear medicine procedure, Tc-99m is bound to a selected
pharmaceutical that transports the Tc-99m to its required location
which is then imaged by radiology equipment. Common nuclear medical
diagnostic procedures include tagging Tc-99m to sulfur colloids for
imaging the liver, the spleen, and bone marrow, to macroaggregated
albumin for lung scanning, to phosphonates for bone scanning, to
iminodiacetic acids for imaging the hepatobiliary system, to
glucoheptonates for renal scanning and brain scanning, to
diethylenetriaminepentaacetic acid (DPTA) for brain scanning and
kidney scanning, to dimercaptosuccinic acid (DMSA) for scanning the
renal cortex, to red blood cells for blood pool scanning of the
heart, to methoxy isoburyl isonitrile (MIBI) for imaging myocardial
perfusion, for cardiac ventriculography, and to pyrophosphate for
imaging calcium deposits in damaged hearts. Tc-99m is also very
useful for detection of various forms of cancer for example, by
identification of sentinal nodes, i.e., lymph nodes draining
cancerous sites such as breast cancer or malignant melanomas by
first injecting a Tc-99m-labeled sulfur colloid followed by
injection of a Tc-99m-labeled isosulfan blue dye.
Immunoscintigraphy methods are particularly useful for detecting
difficult-to-find cancers, and are based on tagging of Tc-99m to
monoclonal antibodies specific to selected cancer cells, injecting
the tagged monoclonal antibodies and then scanning the subject's
body with radiology equipment.
[0003] The world's supply of Tc-99m for nuclear medicine is
currently produced in nuclear reactors. First, the parent nuclide
of Tc-99m, molybdenum-99 (referred to hereinafter as Mo-99) is
produced by the fission of enriched uranium in several nuclear
reactors around the world. Mo-99 has a relatively long half life of
66 hours which enables its world-wide transport to medical centers.
Mo-99 is distributed in the form of Mo-99/Tc-99m generator devices
using column chromatography to extract and recover Tc-99m from the
decaying Mo-99. The chromatography columns are loaded with acidic
alumina (Al.sub.2O.sub.3) into which is added Mo-99 in the form of
molybdate, MoO.sub.4.sup.2-. As the Mo-99 decays, it forms
pertechnetate TcO.sub.4.sup.-, which because of its single charge
is less tightly bound to the alumina column inside of the generator
devices. Pulling normal saline solution through the column of
immobilized Mo-99 elutes the soluble Tc-99m, resulting in a saline
solution containing the Tc-99m as the pertechnetate, with sodium as
the counterbalancing cation. The solution of sodium pertechnetate
may then be added in an appropriate concentration to the
organ-specific pharmaceutical "kit" to be used, or sodium
pertechnetate can be used directly without pharmaceutical tagging
for specific procedures requiring only the [Tc-99m]O.sub.4.sup.- as
the primary radiopharmaceutical.
[0004] The problem with fission-based production of Tc-99m is that
the several nuclear reactors producing the world-wide supply of
Mo-99 are close to the end of their lifetimes. Almost two-thirds of
the world's supply of Mo-99 currently comes from two reactors: (i)
the National Research Universal Reactor at the Chalk River
Laboratories in Ontario, Canada, and (ii) the Petten nuclear
reactor in the Netherlands. Both facilities were shut-down for
extended periods of time in 2009-2010 which caused a serious
on-going world-wide shortage of supply of Mo-99 for medical
facilities. Although both facilities are now active again,
significant concerns remain regarding reliable long-term supply of
Mo-99.
[0005] It is known that medical cyclotrons can produce small
amounts of Tc-99m from Mo-100 for research purposes. It has been
recently demonstrated that Tc-99m produced in a cyclotron is
equivalent to nuclear Tc-99m when used for nuclear medical imaging
(Guerin et al., 2010, Cyclotron production of .sup.99mcTc: An
approach to the medical isotope crisis. J. Nucl. Med.
51(4):13N-16N). However, analyses of numerous studies reporting
conversion of Mo-100 to Tc-99m show considerable discrepancies
regarding conversion efficiencies, gamma ray production, and purity
(Challan et al., 2007, Thin target yields and Empire II predictions
in the accelerator production of technetium-99m. J. Nucl. Rad.
Phys. 2:1-; Takacs et al., 2003, Evaluation of proton induced
reactions on .sup.100Mo: New cross sections for production of
.sup.99mTc and .sup.99Mo. J. Radioanal. Nucl. Chem. 257: 195-201;
Lebeda et al., 2012, New measurement of excitation functions for
(p,x) reactions on .sup.natMo with special regard to the formation
of .sup.95mTc, .sup.96m+gTc, .sup.99m Tc and .sup.99Mo. Appl.
Radiat. Isot. 68(12): 2355-2365; Scholten et al., 1999, Excitation
functions for the cyclotron production of .sup.99m Tc and
.sup.99Mo. Appl. Radiat. Isot. 51:69-80).
SUMMARY OF THE DISCLOSURE
[0006] The exemplary embodiments of the present disclosure pertain
to processes for the production of technetium-99m (Tc-99m) from
molybdenum-100 (Mo-100) by proton irradiation with accelerators
such as cyclotrons. Some exemplary embodiments relate to systems
for working the processes of present disclosure. Some exemplary
embodiments relate to apparatus comprising the systems of the
present disclosure.
DESCRIPTION OF THE DRAWINGS
[0007] The present disclosure will be described in conjunction with
reference to the following drawings in which:
[0008] FIG. 1 is a schematic flowchart outlining an exemplary
process of the present disclosure;
[0009] FIG. 2 is plan view of an exemplary elongate target plate
according to one embodiment of the present disclosure;
[0010] FIG. 3A is a cross-sectional side view and FIG. 3B is a
cross-sectional end view of the exemplary target plate from FIG.
2;
[0011] FIG. 4 is a perspective view of an exemplary target capsule
apparatus for mounting therein the exemplary target plate shown in
FIGS. 2, 3A, 3B;
[0012] FIG. 5 is a partial view into the top of the target capsule
apparatus from FIG. 4;
[0013] FIG. 6 is a cross-sectional side view of the target capsule
apparatus from FIG. 5;
[0014] FIG. 7 is a perspective view of an exemplary target pickup
apparatus with a pusher component for engaging the target capsule
assembly apparatus in FIGS. 4-6;
[0015] FIG. 8 is a cross-sectional side view of the target pickup
apparatus from FIG. 7 engaged with the pusher component;
[0016] FIG. 9 is a perspective view of an exemplary receiving cell
apparatus for engaging and cooperating with the target station
apparatus shown in FIGS. 12-14;
[0017] FIG. 10 is a side view of the receiving cell apparatus shown
in FIG. 9;
[0018] FIG. 11 is a top of the receiving cell apparatus shown in
FIG. 9;
[0019] FIG. 12 is a perspective view of an exemplary target station
apparatus for receiving the target pickup apparatus shown in FIGS.
7-8 engaged with the target capsule apparatus shown in FIGS.
4-6;
[0020] FIG. 13 is a side view of the target station apparatus shown
in FIG. 12;
[0021] FIG. 14 is a top view of the target station apparatus shown
in FIG. 12;
[0022] FIG. 15A is a plan view of an exemplary circular target
plate according to one embodiment of the present disclosure, FIG.
15B is a top view, and FIG. 15C is a cross-sectional side view of
the exemplary circular target plate from FIG. 15A;
[0023] FIG. 16 is a perspective view of an exemplary target capsule
apparatus for mounting therein a circular target disc;
[0024] FIG. 17 is an end view of the target capsule apparatus shown
in FIG. 16;
[0025] FIG. 18 is a cross-sectional side view of the target capsule
apparatus shown in FIG. 16;
[0026] FIG. 19 is a perspective view of an exemplary target pickup
apparatus engaged with a pusher component;
[0027] FIG. 20 is a cross-sectional side view of the target pickup
apparatus from FIG. 19;
[0028] FIG. 21 is a perspective view of an exemplary receiving cell
apparatus for engaging and cooperating with the target station
apparatus shown in FIGS. 24-27;
[0029] FIG. 22 is a side view of the receiving cell apparatus shown
in FIG. 21;
[0030] FIG. 23 is a top view of the receiving cell apparatus shown
in FIG. 21;
[0031] FIG. 24 is a perspective view of an exemplary target station
apparatus for receiving the target pickup apparatus shown in FIG.
19 engaged with the target capsule apparatus shown in FIGS.
16-18;
[0032] FIG. 25 is a top view of the target station apparatus shown
in FIG. 24;
[0033] FIG. 26 is a cross-sectional top view of the target station
apparatus shown in FIG. 24 with an exemplary target cell apparatus
delivered to the target housing in an unloaded position;
[0034] FIG. 27 is across-sectional top view of the target station
apparatus shown in FIG. 24 with the exemplary target cell apparatus
moved to a loaded position;
[0035] FIG. 28 is a perspective view of an exemplary booster
station; and
[0036] FIG. 29A is a perspective view of the exemplary booster
station from FIG. 28 with the cover removed and in a disengaged
view, while FIG. 29B shows the booster station in an engaged
mode.
DETAILED DESCRIPTION
[0037] An exemplary embodiment of the present disclosure pertains
to processes for producing Tc-99m by low-energy proton radiation of
Mo-100 using proton beams produced by accelerators such as
cyclotrons. Suitable proton energy for the processes of the present
disclosure is from a range of about 10 MeV to about 30 MeV incident
on the target. A flowchart outlining an exemplary process is shown
in FIG. 1. The process generally follows the steps of:
[0038] 1) Processing a supply of enriched Mo-100 metal powder to
produce a Mo-100 powder with a consistent grain size of less than
about 10 microns.
[0039] 2) Depositing a coating of the processed Mo-100 powder onto
a target plate comprising a transition metal, by electrochemical
and/or electrophoretic deposition.
[0040] 3) Sintering the coated target plate in an inert atmosphere
for about 2 hours to about 10 hours at a temperature of about
1200.degree. C. to about 2000.degree. C.
[0041] 4) Securely engaging the sintered target plate into a target
holder. A target holder engaged with a sintered target plate is
referred to herein as a target capsule assembly.
[0042] 5) Installing the target capsule assembly into a receiving
cell apparatus wherein the target capsule assembly is engaged by a
target pickup apparatus. The target pickup cooperates with a target
transfer drive apparatus for delivery of the target capsule
assembly into a target station apparatus engaged with a
cyclotron.
[0043] 6) In an atmosphere that is substantially oxygen-free,
irradiating the sintered target plate with a supply of protons
generated by an accelerator.
[0044] 7) With a transfer drive apparatus, disengaging the target
capsule assembly from the target station and transferring the
target capsule assembly into receiving cell apparatus for
separating and recovering molybdate ions and pertechnetate ions
from the proton-irradiated target plate.
[0045] 8) Separating the pertechnetate ions from the molybdate
ions, purifying, and further processing the pertechnetate ions.
These steps are done under precisely controlled environmental
conditions to minimize losses of the pertechnetate ions.
[0046] 9) Recovering and purifying the molybdate ions to make them
suitable for re-use in coating target plates.
[0047] Previous uses of accelerators for producing Tc-99m from
Mo-100 were focused on producing small quantities of product
sufficient for research use and for comparison of thus-produced
Tc-99m functionality in medical diagnostic imaging with the
standard Tc-99m produced from Mo-99 using nuclear reactors.
Commercially available enriched Mo-100 metal powders typically
comprise mixtures of particle sizes ranging from less than a micron
to more than a millimeter. Consequently, using such powders for
coating target backing discs or backing plates results in uneven
distribution of Mo-100 across the plate surfaces and varying
thicknesses of Mo-100 deposition. Such variabilities result in
target plate failures during irradiation with proton beams, in
lowered conversion efficiencies of molybdenum atoms into technetium
atoms, and in unpredictable yields of pertechnetate ions.
Accordingly, it has become common practice to press
commercial-grade Mo-100 powders at pressures of about 25,000 N to
about 100,000 N into pellets having diameters in the range of 6.0
to 9.5 mm. The Mo-100 pellets are then reduced in a hydrogen
atmosphere at temperatures in the range of 800.degree. C. to
900.degree. C. Mo-100 is typically mounted onto a target backing
disc either as commercial-grade Mo-100 powders or alternatively as
sintered Mo-100 pellets by pressing, or by arc melting, or electron
beam melting. The melting methods generally use currents from a
range of 40 mA to 70 mA which are applied in a variety of sweeping
patterns and focusing patterns. Consequently, using such powders
and/or pellets for coating target plates results in uneven
distribution of Mo-100 across the plate surfaces and in varying
thicknesses of Mo-100 deposition. Such variabilities result in: (i)
target plate failures during irradiation with proton beams, (ii) in
lowered conversion efficiencies of molybdenum atoms into technetium
atoms, and (iii) in unpredictable yields of pertechnetate ions.
Other problems commonly encountered are associated with the target
discs themselves. The targets typically used in the research-scale
Tc-99m production in cyclotrons comprise small thin discs of copper
or tantalum having diameters generally in the range of about 5-6
mm. Such discs can not be loaded with sufficient Mo-100 to enable
large-scale production of Tc-99m, because they are mechanically
fragile and may fail, i.e., fragment, under proton irradiation due
to the very high levels of heat concomitantly generated. There are
numerous challenges and issues that must be addressed in order to
successfully scale Tc-99m production from Mo-100 using
cyclotron-based systems. Issues related to the molybdenum that need
to be addressed include overcoming the problems of: (i) inability
to deposit thick layers of Mo-100 onto target plates by galvanic
plating from aqueous solutions, (ii) isotopically enriching
molybdenum to facilitate production of specific technetium
isotopes, and (iii) requirements for concentrated acid solutions
and for extended periods of time for dissolving irradiated plates
of molybdenum. Challenges that need to be solved to facilitate
commercial-scale production of Tc-99m production from Mo-100 using
cyclotron-based systems, include selection of and configuring of
suitable target backing plate materials: (i) to which Mo-100 will
strongly adhere to before and during proton irradiation, (ii) that
are impervious to penetration by protons, (iii) that are
sufficiently mechanically robust to withstand heating during proton
irradiation, (iv) that are thin enough to enable heat dissipation
and/or cooling of the Mo-100 during irradiation, and (iv) are
chemically inert, i.e., will not chemically contaminate or
otherwise interfere with dissolution of the irradiated Mo-100.
[0048] Accordingly, some exemplary embodiments of the present
disclosure relate to a process for refining commercial Mo-100
powders into uniform particles of less than 10 microns, to
mechanically robust target plates for mounting thereon of the
refined Mo-100 particles, and to electrophoretic methods for
mounting the refined Mo-100 particles onto the targets plates.
[0049] According to one aspect, commercial-grade Mo-100 metal
powder is first oxidized in a solution comprising about 3% to about
40% hydrogen peroxide (H.sub.2O.sub.2). A particularly suitable
concentration of H.sub.2O.sub.2 is about 30%. The mixture of Mo-100
and H.sub.2O.sub.2 is then heated to a range of about 40.degree. C.
to about 50.degree. C. to denature residual H.sub.2O.sub.2, then
dried to recover solid molybdenum oxide. The solid molybdenum oxide
is converted back to Mo-100 metal using a three-stage heating
process. In the first stage, the dried molybdenum oxide is heated
for about 30 min at about 400.degree. C. in an environment
comprising about 2% hydrogen in an argon gas mixture to allow for
the formation of MoO.sub.3. After 30 min at 400.degree. C., the
temperature is then raised for the second stage of the process, to
about 700.degree. C. for about 30 min to facilitate the reduction
of MoO.sub.3 to MoO.sub.2. The temperature is then further raised
for the third stage of the process, to about 1100.degree. C. for
about 30 min to reduce the MoO.sub.2 to Mo-100 metal. Because
MoO.sub.2 sublimes at 1500.degree. C., it is important to keep the
temperature during the third stage within the range of about
1100.degree. C. and about 1455.degree. C., of about 1100.degree. C.
and about 1400.degree. C., of about 1100.degree. C. and about
1350.degree. C., of about 1100.degree. C. and about 1300.degree.
C., of about 1100.degree. C. and about 1250.degree. C., of about
1100.degree. C. and about 1200.degree. C. It is important to limit
the atmospheric hydrogen content during the first stage of the
process less than about 5%, about 4%, about 3%, and preferably at
about 2% or less to control the rate of reduction of MoO.sub.3 to
MoO.sub.2. Because the reduction of MoO.sub.2 to Mo-100 is an
endothermic reaction, it is suitable to use a high hydrogen
atmosphere, or alternatively, a pure hydrogen atmosphere for the
third stage of this process. The processed Mo-100 powder produced
by this three-stage process is characterized by a consistent grain
size of less than 10 microns.
[0050] Another aspect of this embodiment of the present disclosure
relates to electrophoretic processes for coating target backing
plates with the refined Mo-100 powders having uniform particle
sizes of less than 10 microns. A refined Mo-100 powder is suspended
in a suitable polar organic solvent exemplified by anhydrous
nitromethane, nitroalkanes, isopropanol, and the like, and a
suitable binder exemplified by zein, and then stirred vigorously at
an ambient temperature selected from a range of about 15.degree. C.
to about 30.degree. C. A cathode comprising a transition metal and
an anode comprising a conductive metal exemplified by copper, are
then submerged into the suspension. A potential of about 150 V to
about 5000 V, about 200 V to about 4000 V, about 250 V to about
3000 V, about 300 V to about 2500 V, about 400 V to about 2000 V,
about 500 V to about 1500 V is applied across the anode and cathode
for a duration of time from about 2 min to about 30 min to cause
deposition of the Mo-100 and the binder onto the cathode. A
particularly suitable potential to apply across the anode and
cathode is about 1200 V. The coated cathodes are then removed from
the mixture and sintered by heating at a temperature from the range
of about 1500.degree. C. to about 2000.degree. C., about
1300.degree. C. to about 1900.degree. C., about 1400.degree. C. to
about 1800.degree. C., about 1400.degree. C. to about 1700.degree.
C., for a period of time from the range of 2-7 h, 2-6 h, 4-5 h in
an oxygen-free atmosphere provided by an inert gas exemplified by
argon. We have discovered that this process enables deposition of a
molybdenum metal layer onto target backing plates (also referred to
herein as "target plates") with a density that is about 85% of the
possible theoretical density.
[0051] Another aspect of this embodiment pertains to target plates
onto which is mountable Mo-100. The target plate configuration is
suitable for irradiation by protons delivered: (i) with or without
a beamline extending from a cyclotron, or alternatively (ii) in a
self-shielded cyclotron chamber wherein beamlines are not used. The
width of the target plate is sufficient to receive an entire
beamspot of proton energy produced with a cyclotron, even when
delivered to the target plate at a selected angle from about
7.degree. to about 90.degree. relative to the incident beam. Beam
spots typically generated in cyclotron beamlines are collimated at
about 15-mm diameter. It is common to place a Mo-100-coated target
plate at an angle to a protein beamline in which case, the
irradiated surface area on the target plate will be an elongate
spot of about 10 mm to about 15 mm by about 20 mm to about 80 mm.
In self-shielded cyclotrons that do not use beamlines, the spaces
for installing target plates are typically about 30 cm.times.30
cm.times.30 cm to by about 30 cm.times.30 cm.times.80 cm.
Accordingly, for large-scale production of Tc-99m, it is desirable
to have target plates that can be used in: (i) cyclotrons using
beamlines such as those exemplified by TR PET cyclotrons
manufactured by Advanced Cyclotron Systems Inc. (ACSI, Richmond,
BC, CA), by Best Cyclotron Systems Inc. (Springfield, Va., USA), by
IBA Industrial (Louvain-la-Neuve, Belgium), and (ii) in
self-shielded cyclotrons that do not use beamlines as exemplified
by GE.RTM.'s PETtrace.RTM. cyclotron systems (GE and PETtrace are
registered trademarks of the General Electric Company, Schenectady,
N.Y., USA). The exemplary target plates may be circular discs for
irradiation by proton beams at a 90.degree. to the target discs, or
alternatively, elongate plates for irradiation by proton beams
delivered angles of less than 90.degree. to the target plates.
[0052] However, a significant problem that occurs during proton
irradiation of Mo-100 is the generation of excessive heat.
Accordingly, it is necessary to coat Mo-100 onto target backing
plates that are good thermal conductors and readily dissipate heat.
The problem with most suitable thermo-conductive metals is that
they have relatively low melting points. Accordingly, there is a
risk that target backing plates comprising a thermo-conductive
metal that have been electophoretically coated with Mo-100, will
melt during the sintering process disclosed herein for increasing
the density of, and making adherent the coated Mo-100 powder. It is
known that tantalum has a very high melting point, i.e., of about
3000.degree. C. and greater. Therefore, it would appear that
tantalum might be a preferred metal substrate for target backing
plate configurations. However, a problem with tantalum is that this
transition metal is not very heat conductive. Therefore, the use of
tantalum for target backing plates requires keeping the target
backing plates as thin as possible in order to provide some cooling
by a coolant flow direct to and about the back of the target
backing plates, while at the same time, providing sufficient
thickness to absorb heat without fracturing or disintegration and
to stop residual protons that may have exited the Mo-100 layer.
Accordingly, we investigated various designs and configurations of
tantalum target backing plates for coating thereonto of Mo-100. One
approach was to machine a series of interconnected channels into
the back of a tantalum target backing plate as exemplified in FIGS.
2 and 3. A flow of coolant is directed through the channels during
proton irradiation, and thus dissipates some of the heat generated.
However, we found that providing channels for coolant flow about
the back of the tantalum target backing plate compromised the
structural strength of the backing plates, i.e., they were quite
flexible and would fracture under the stresses of coolant flow and
proton irradiation. We have surprisingly discovered that the
sintering process to densify an make adherent Mo-100 coated onto
such tantalum target backing plates, also significantly hardens the
tantalum substrate thereby making target backing plates
mechanically robust and extremely durable in use during proton
irradiation and concurrent pressurized circulation of a coolant
about the back of the target backing plate through the channels
provided therefore. We have determined that sintered Mo-100-coated
target plates comprising tantalum are robust and are structurally
stable when irradiated with over 130 microamps of 16.5 MeV protons,
and when irradiated with over 300 microamps of 18.5 MeV protons
while temperature is maintained at or below about 500.degree. C. by
a pressurized flow of a coolant about the back of the target
backing plates.
[0053] The mass of Mo-100 required to produce a suitable target
will depend on the size of the proton beam spot. The target should
at least match or exceed the proton beam spot size. The density of
Mo-100 is about 10.2 g/cm.sup.3. Accordingly, the mass of Mo-100
required to coat a target plate will be about "density of
Mo-100.times.area of the target.times.thickness required" and is
calculated for the type of beam line used i.e., for orthogonal
irradiation or alternatively, for irradiation by proton beams
delivered at angles of less than 90.degree. to the target plates.
It is to be noted that the mass of Mo-100 required will not be
affected by delivery of protons at an angle to the target because
the required thickness of the coating decreases at the same rate as
the surface area increases, since only one axis of the beam
projection is extended as a consequence of changing the angle of
the target to the beam.
[0054] Table 1 provides a listing of the target thicknesses of
molybdenum for deposition onto circular target plates for
orthogonal irradiation with a proton beam (i.e., at about
90.degree. to the plate) for each of three irradiation energies
commonly used by cyclotrons.
TABLE-US-00001 TABLE 1 Entrance energy (MeV) Exit energy (MeV)
Range (.mu.m) 16.5 10 313 18 10 401 22 10 664
[0055] Table 2 provides a listing of the target thicknesses of
molybdenum for deposition onto elongate target plates for proton
irradiation at different angles to the target for each of the three
irradiation energies listed in Table 1.
TABLE-US-00002 TABLE 2 Required thickness (.mu.m) Angle 22-10 MeV
18-10 MeV 16.5-10 MeV 90 664 401 313 85 661 399 312 80 654 395 308
75 641 387 302 70 624 377 294 65 602 363 284 60 575 347 271 55 544
328 256 50 509 307 240 45 470 284 221 40 427 258 201 35 381 230 180
30 332 201 157 25 281 169 132 20 227 137 107 15 172 104 81 10 115
70 54 7 81 49 38
[0056] An exemplary target plate 10 is shown in FIGS. 2-3, and has
an elongate shape with rounded opposing ends. FIG. 2 is a top view
of the exemplary target plate 10. FIG. 3A is a cross-sectional side
view of the target plate 10, and FIG. 3B is a cross-sectional end
view of the target plate 10. The thickness of the target plate 10
is sufficient to stop the entire proton beam at the maximum energy
of 19 MeV, when no molybdenum is present. However, because of the
high heat generated during proton irradiation, water channels 12
are provided in the underside of the target plate 10 to enable the
circulation of a coolant underneath the target plate 10, to
dissipate the excess heat. When coated with Mo-100, the target
plate is capable of dissipating 300 .mu.A of 18 MeV protons when
delivered in an elliptical beam spot of about 10 mm by about 20 mm
at an angle of 10.degree. to the target plate while maintaining
temperatures at about or below 500.degree. C.
[0057] This exemplary target plate is about 105 mm long by 40 mm
wide by 1.02 mm thick. The cathode i.e., the target plate can
comprise any transition metal such as those exemplified by copper,
cobalt, iron, nickel, palladium, rhodium, silver, tantalum,
tungsten, zinc, and their alloys. Particularly suitable are copper,
silver, rhodium, tantalum, and zinc. It is to be noted that if
tantalum is used as the target plate material, the sintering
process will also significantly harden the tantalum target plate
making it extremely durable and able to withstand fracturing
stresses resulting from proton irradiation and/or excessive heat
produced during proton irradiation and the pressurization due to
the flow of coolant about the back of the target plate.
[0058] Another problem that must be addressed during production of
Tc-99m from Mo-100 is preventing Mo-100 coated onto a target plate,
from oxidizing during and after irradiation with proton beams.
Molydenum oxide has a significant vapor pressure at only a few
hundred .degree. C. and consequently, exposure to high heat and
oxygen during proton irradiation will result in the formation of
molybdenum oxide resulting in decreases in the conversion
efficiency of Mo-100 to Tc-99m.
[0059] Accordingly, some exemplary embodiments of the present
disclosure relate to a system comprising: (i) components for
mounting and housing Mo-100-coated target plates, these components
referred to hereinafter as "target capsule assemblies" or "target
capsule apparatus", and (ii) components for engaging and
disengaging the target capsule assemblies with sources of proton
irradiation generated by cyclotrons while maintaining an
oxygen-depleted atmosphere about the Mo-100-coated target plates
mounted therein. Accordingly, the system and components disclosed
herein are configured to enable isolation of a Mo-100-coated target
plate from exposure to oxygen during irradiation with protons, by
the provision and maintenance of atmospheric environments that are
substantially oxygen-free. The oxygen-free environments can be
provided by application and maintenance of a vacuum during and
after irradiation. Alternatively, the environments can be saturated
with ultra-high purity inert gases.
[0060] The following portion of the disclosure with references to
FIGS. 4-14 pertains to the use of the exemplary embodiments and
aspects of the present disclosure for irradiation of Mo-100-coated
target plates with protons delivered in a beamline to the target
plates at an angle of less than 90.degree.. Such beamlines are
available PET cyclotrons exemplified by those manufactured by
ACSI.
[0061] One aspect relates to a target capsule apparatus for
mounting therein a Mo-100-coated target plate. Another aspect
relates to a target capsule pickup apparatus for remote engagement
of the target capsule and for conveying the capsule assembly to and
engaging it with a target station apparatus. Another aspect relates
to a target station apparatus comprising a vacuum chamber for
engaging therein the assembled and engaged target capsule apparatus
and target pickup apparatus. The target station apparatus is
sealingly engagable with a source of protons from an accelerator
such as those exemplified by cyclotrons.
[0062] An exemplary elongate target capsule apparatus for mounting
therein an elongate Mo-100-coated target plate for irradiation with
protons delivered at an angle of less than 90.degree. by PET
cyclotrons exemplified by those manufactured by ACSI, is shown in
FIGS. 4-6. This exemplary target capsule apparatus 20 comprises a
bottom target plate holder 21 and a top cover plate 22 provided
with a plurality of spaced-apart bores 23 through which socket-head
cap screws 24 are inserted and threadably engaged with the bottom
target plate holder 21. The elongate target capsule apparatus 20
has a proximal end 25 for engagement with a target capsule pickup
apparatus, and a distal end 26 having a bore 26a for receiving an
emission of protons from a suitable accelerator (not shown). The
distal end 26 of the target capsule apparatus 20 also has two ports
26b for sealingly engaging a supply of a chilled coolant flow that
is directed by channel 27 to contact and flow underneath target
plate 10 through channels 12 provided in the undersurface of the
target plate 10 (refer to FIGS. 3(a) and (b)). The upper surface of
the bottom target plate holder 21 may be inclined at an angle from
a range of about 5.degree. to about 85.degree. relative to a
horizontal plane. The lower surface of the top cover plate 22 is
inclined at a matching angle to the upper surface of the bottom
target plate holder 21. An elongate target plate 10 is placed on
top of O-rings 28 fitted into channels provided therefore in the
upper surface of the bottom target plate holder 21. O-rings 28 are
also fitted into channels provided therefore in the lower surface
of the top cover plate 22. The O-rings 28 securely and sealingly
engage the elongate target plate 10 between the bottom target plate
holder 21 and the top cover plate 22 when the socket-head cap
screws 24 are inserted through the spaced-apart bores 23 and are
threadably engaged with the bottom target plate holder 21. The
shape of the outer diameter of the proximal end (25) of the target
capsule apparatus 20 is to engage with rollers (not shown) provided
therefor in the target station and to rotate the target capsule
apparatus 20 to align the ports 26a, 26b with the target station to
form the vacuum and water seals. The symmetrical configuration of
the target capsule apparatus 20 makes it possible to rotate the
apparatus 20 in a clockwise direction or in a counter-clockwise
direction. The coolant can ingress the target capsule apparatus 20
through either of ports 26b and egress through the opposite port
26b.
[0063] An exemplary target pickup apparatus 40 is shown in FIGS.
7-8. The target pickup apparatus 40 comprises a pickup head device
41 configured for engaging with and disengaging from chamber 25a
provided therefor in the proximal end 25 of the target capsule
apparatus 20 shown in FIGS. 4-6. The pickup head device 41 is
provided with structures that radially extend and retract from
within the pickup head configured to engage and disengage with the
chamber 25a in the proximal end 25 of the target plate capsule
apparatus 20. Suitable engagement devices are exemplified by pins,
prongs, struts and the like. FIG. 8. shows extendible/retractable
prongs 43. The target pickup apparatus 40 is also provided with a
target capsule apparatus pusher 44 that is engagable and
disengagable by the engagement devices exemplified by prongs 43.
The extendible/retractable prongs 43 provided in the pickup head
device 41 are actuated and manipulated by a remotely controllable
pull ring 49 mounted onto a coupling shaft 48 extending backward
from the pickup head device 41. The target pickup apparatus 40
additionally comprises a target pickup guide 46 provided with
forward extending shaft 47 that is slidingly received and engaged
with the coupling shaft 48 extending backward from the pickup head
device 41. The rear of the target pickup guide 46 cooperates with
an engagable/disengagable steel tape (shown as a shaft 50 in dashed
lines in FIG. 8) that cooperates with the target pickup apparatus
40 for delivery of a target capsule apparatus 20 from a target
station receiving cell apparatus 80 (See FIG. 9) to a target
station apparatus (shown as item 58 in FIG. 12), and then for
post-irradiation recovery of the target capsule assembly 20 from
the target station apparatus 58 and delivery back to the target
station receiving cell apparatus 80.
[0064] FIGS. 9-11 show an exemplary target station receiving cell
apparatus 80 that is installable in a lead-lined fume hood.
Suitable lead-lined fume hoods are exemplified by "hot cells"
available from Von Gahlen International Inc. (Chatsworth, Ga., USA)
and from Comecer Inc. (Miami, Fla., USA). The target station
receiving cell apparatus 80 comprises a framework 82 onto which are
mounted an upper shelf 83 and a lower shelf 84. A drive unit
assembly 85 is mounted onto the upper shelf 83. The drive unit
assembly 85 houses a length of steel tape 50 that is rolled up onto
a drum (not shown) housed within the drive unit assembly 85. The
proximal end of the steel tape 50 is engaged with a drum (not
shown) provided within the drive unit assembly 85, while the distal
end of the steel tape 50 is coupled with the target pickup
apparatus 40 as shown in FIG. 8. The drive assembly has: (i) a
first one-way clutch and gear assembly 81 that is engaged with the
drum, (ii) a second one-way clutch and gear assembly 86 that is
controllably engagable with the steel tape extending therethrough,
and (iii) a drive motor 99 that cooperates with a chain (not shown)
to provide a driving force to the first one-way clutch and gear
assembly 81 and the second one-way clutch and gear assembly 86. The
distal end of the steel tape is coupled to the pickup head device
41 of the target pickup apparatus 40 and extends downward within
the target leading tube 95 when not in use. The target pickup
apparatus 40 is deployed and recovered through a target leading
tube 95 by the operation of the drive unit assembly 85. A gate
valve assembly 100 is mounted onto a port in the hot cell (not
shown) directly underneath the target leading tube 95. The gate
valve (not shown) within gate valve assembly 100 is opened and
closed by actuator 101. Mounted onto the lower shelf 84 are
carriage rails 115 on which is conveyed backward and forward a
docking station carriage table 114. A docking station 110 is
mounted onto the docking station carriage table 114. The docking
station 110 is moveable sideways by a pair of linear actuators 116.
The docking station comprises a housing having three linearly
aligned bores 111, 112, 113. Bore 111 is a through hole for
connecting the lower end of target leading tube 95 with the top of
the gate valve assembly 100. Bore 112 is provided to receive and
store the target capsule apparatus pusher 44 component of the
target pickup apparatus 40, when it is not in use. Bore 113 is
provided to receive an assembled target capsule assembly 20 with
its proximal end 25 in an upward position.
[0065] In use, within a hot cell using remote-controlled devices
(not shown), a Mo-100-coated target plate 10 is mounted into a
target capsule assembly 20. The loaded target capsule assembly 20
is placed by the remote-controlled devices into the target capsule
assembly receiving bore 113 while the target docking station
carriage table 114 is positioned by remote control forward and
clear of upper shelf 83. Target docking station carriage table 114
is then driven by remote control to a position under upper shelf 83
such that the linearly aligned bores 111, 112, 113 are centrally
aligned with the gate valve assembly 100. The docking station 110
is then conveyed sideways to precisely position bore 113 underneath
the target leading tube 95 thus being simultaneously directed above
gate valve assembly 100. The transfer drive unit assembly 85 is
then operated to deploy sufficient steel tape to engage the target
pickup mechanism 41 with the target capsule apparatus 20, and then,
the transfer drive unit assembly 85 is reversed to draw the target
capsule apparatus 20 up into target leading tube 95. Then, the
docking station 110 is moved to align bore 111 with the target
leading tube 95 thus being simultaneously positioned directly above
gate valve assembly 100, after which, actuator 101 is operated to
open the gate valve. Release actuator 96 is operated to release the
target capsule 20 from the target pickup mechanism 41 allowing the
target capsule 20 to fall through the bore of gate valve assembly
100 and into transfer tube 68. Then, docking station 110 is moved
so that target capsule pusher receiving bore 112 is directly under
the target leading tube 95. The transfer drive 85 is operated to
engage the target capsule apparatus pusher 44 by deploying steel
tape from the drum within the transfer drive 85 by the pinch
rollers 104 in cooperation with the pinch roller linear actuator
103, the pinch roller cam linkage 105, and the second one-way
clutch and gear assembly 86, so that prongs 43 in the pickup head
device 41 of the target pickup apparatus 40 engage the target
capsule apparatus pusher 44. The first one-way clutch and gear
assembly 81 is disengaged and operates freely when the second
one-way clutch and gear assembly is engaged. The target pickup
apparatus 40 engaged with the pusher 44 is then drawn up into
target leading tube 95 by disengaging the pinch rollers 104 by
operating the pinch roller linear actuator 103 in cooperation with
pinch roller cam linkage 15, and then re-winding the steel tape
onto the drum of the transfer drive apparatus 85 with the first
one-way clutch and gear assembly 81 in cooperation with the drive
motor 99. The second one-way clutch and gear assembly 86 is
disengaged and operating freely during this operation. The docking
station 110 is then moved so that bore 111 is directly under the
target leading tube 95. The transfer drive apparatus 85 is then
operated to deploy the steel tape by the pinch rollers 104 in
cooperation with the pinch roller linear actuator 103 and the
second one-way clutch 86 (first one-way clutch and gear assembly 81
is disengaged and operates freely) so that the target pickup
apparatus 40 with the pusher 44 pushes the target capsule assembly
20 through the transfer tube 68 to deliver the target capsule
assembly 20 to a target station assembly (shown as 58 in FIGS.
12-14) that is operably coupled to a cyclotron.
[0066] FIGS. 12-14 show an assembly 58 of an exemplary target
station apparatus 60 coupled by a spigot flange 66 to a vacuum
chamber apparatus 70 that is engaged with a beam line to an
accelerator such as a cyclotron (not shown). The assembly is
mounted into the facility by framework 59. The target station
apparatus 60 is connected to a transfer tube 68 by a transfer tube
mount 69. The other end of the transfer tube 68 is engaged with the
flange 120 of the gate valve assembly 100 mounted into the
receiving cell apparatus 80 shown in FIGS. 9-11. The target station
apparatus 60 comprises a housing wherein is delivered the elongate
target capsule apparatus 20 (shown in FIGS. 4-6) by the target
pickup apparatus 40 shown in FIGS. 7-8. A linear drive unit 65
mounted onto the target station apparatus 60 engages two rollers
(not shown) that contact the outer diameter of the proximal end of
target capsule assembly 20 and cooperate with the curved surface of
the outer diameter to rotate the target capsule apparatus 20 so
that it is aligned with spigot flange 66. After it is aligned, the
target capsule apparatus 20 is then moved by the linear drive unit
65 to sealably engage spigot flange 66 thereby forming a
vacuum-tight connection between target capsule port 26a with the
vacuum chamber apparatus 70 and two water-tight connections with
target capsule ports 26b. Target capsule assembly 20 may engage
with spigot flange 66 in either of two positions 180 degrees apart
because both positions are operationally identical. The loaded
target capsule assembly 20 is now ready for proton irradiation. The
vacuum chamber 70 is evacuated by suitable vacuum pumps (not shown)
interconnected to a vacuum port 73. The proton beam is collimated
during the irradiation process by four proton beam collimator
assemblies 71 mounted about the vacuum chamber 70. The passage of
the proton beam is limited in position by baffle 72 such that the
protons are only incident on the collimators or target plate 10 of
target capsule assembly 20.
[0067] After proton irradiation is complete, the beamline is
isolated from the vacuum chamber 70 with the aforementioned vacuum
valve and the vacuum chamber pressure is raised to atmospheric
pressure. The cooling water is purged out of the target capsule 20.
The irradiated target capsule assembly 20 is disengaged from spigot
flange 66 by linear actuator 65 and then recovered by engaging the
pickup head device 41 of target pickup apparatus 40 with the
chamber 25a in the proximal end of the target capsule assembly 20.
The target capsule assembly 20 is then delivered back to the target
station receiving cell apparatus 80 by recovery of the deployed
steel tape 50 by the drive unit assembly 85 until the target
capsule unit egresses from the transfer tube 68 and out of the gate
valve assembly 100. The docking station 110 is then conveyed to
position precisely bore 113 underneath the target leading tube 95,
after which the irradiated target capsule assembly 20 is deposited
into the target capsule assembly receiving bore 113 and disengaged
from the target pickup apparatus 40. The target pickup apparatus 40
is then retracted into the target leading tube 95, and the docking
station 110 moved back to its resting position. As will be
described in more detail later, the pertechnetate ions and
molybdenate ions are dissolved from the irradiated target plate in
an apparatus provided therefore in the hot cell, recovered and then
separately purified.
[0068] Another embodiment of the present disclosure pertains to
systems comprising components for mounting and housing circular
Mo-100-coated target plates, and components for engaging and
disengaging the housed circular target plates with sources of
proton irradiation generated by cyclotrons while maintaining an
oxygen-depleted atmosphere about the mounted Mo-100-coated target
plates.
[0069] An exemplary circular target plate 140 is shown in FIGS.
15A-15C. FIG. 15A is a perspective view from the top of the
circular target plate 140 and shows a recessed section 145 about
the centre of the circular target plate 140. FIG. 15B is a top view
of the circular target plate 140, while FIG. 15C is a
cross-sectional side view of the circular target plate 140. The
circular target plate 140 may comprise any transition metal such as
those exemplified by copper, cobalt, iron, nickel, palladium,
rhodium, silver, tantalum, tungsten, zinc, and their alloys.
Particularly suitable are copper, silver, rhodium, tantalum, and
zinc. The recessed portion 145 is provided for receiving therein a
refined Mo-100 metal powder, which is then sintered as previously
described.
[0070] FIGS. 16-18 show an exemplary capsule apparatus 200 for
positioning and mounting therein a Mo-100-coated circular target
plate 199 that does not have a recess, or alternatively, a circular
target plate with a recess as exemplified in FIGS. 15A-15C. FIG. 16
is a perspective view, FIG. 17 is an end view with target plate 140
removed, and FIG. 17 is a cross-sectional side view of the capsule
apparatus 200 that generally comprises an outer housing 205, an
inner cooling distributor 215 (also referred to as a cooling
sleeve) for receiving and retaining therein the Mo-100-coated
circular target plate 199, and housing clamping nut 210 for
securely engaging the cooling sleeve and circular target plate 140.
O-rings 219 are inserted interposed the target plate 199, the outer
housing 205, the inner cooling distributor 215, and the housing
clamping nut 210 to sealably secure the target plate 199 into the
capsule apparatus 200. The purpose of the cooling sleeve 215 is to
controllably dissipate heat that is generated by proton irradiation
of the Mo-100-coated target plate 140 thereby minimizing the
potential for heat-generated oxidation of molybdenum atoms and
technetium atoms. The capsule housing clamping nut 210 comprises a
chamber 212 configured for engaging and releasing a target pickup
apparatus (shown as item 220 in FIG. 19).
[0071] Another aspect of this embodiment pertains to an exemplary
target capsule pickup apparatus 220 for engaging and manipulating
an assembled circular target plate capsule apparatus (FIGS. 19-20).
FIG. 19 is a perspective view while FIG. 20 is a cross-sectional
side view of the target capsule pickup apparatus 220 engaged with a
pusher 225. The target capsule pickup apparatus 220 generally
comprises a radially extendable/retractable pickup head device 223
for engaging an assembled target plate capsule apparatus 200 or
pusher 225, a shaft 226 extending backward from the pickup head for
engaging a shaft 231 extending forward from a target pickup guide
230. Shaft 231 extends backward through a target pickup guide 230
and engages a steel tape 232. The target capsule pickup apparatus
220 additionally comprises a target housing pusher 225 for
delivering the target capsule apparatus 200 into a target station
apparatus (shown in FIGS. 24-27). The shaft 226 extending backward
from the pickup head device 223 is provided with an actuating
device 227 to radially extend and retract engagement devices 224
within the pickup head device 223 that are configured to engage and
disengage with the assembled target plate housing apparatus.
Suitable engagement devices are exemplified by pins, prongs, struts
and remotely actuated and manipulated by remote control of
actuating device 227.
[0072] Another aspect of this embodiment pertains to an exemplary
target station apparatus for receiving and mounting therein an
assembled circular target plate capsule apparatus, and then
engaging the circular target plate capsule apparatus with a proton
beam port on a cyclotron exemplified by GE.RTM.'s PETtrace.RTM.
cyclotron systems. The target station assembly has multiple
purposes, i.e., (i) receiving and mounting the assembled target
plate capsule apparatus into a vacuum chamber, (ii) establishing a
stable oxygen-free environment within vacuum chamber by application
of a vacuum and/or replacement of the atmospheric air with an
ultra-high purity inert gas exemplified by helium, (iii) delivering
the assembled target plate capsule apparatus to a source of
cyclotron generated proton energy and engaging the target plate
capsule apparatus with the source of proton emission, (iv)
establishing and maintaining a vacuum seal between the target plate
capsule apparatus and the source of proton emission, (v) precisely
manipulating the temperature of the cooling distributor in the
housing apparatus during the irradiation operation, (vi)
disengaging and removing the irradiated target plate capsule
apparatus from the source of proton emission.
[0073] FIGS. 21-24 show another exemplary target station receiving
cell apparatus 300 that is installable in a lead-lined fume hood
(also referred to as a hot cell). The receiving cell apparatus 300
comprises a framework 305 onto which are mounted an upper shelf 306
and a lower shelf 307. A drive unit assembly 310 is mounted onto
the upper shelf 306. The drive unit assembly 310 houses a length of
steel tape 232 rolled up onto a drum (not shown) that is housed
within the drive unit assembly 310. The steel tape 232 is deployed
and recovered through a target leading tube 315 that is
interconnected to the drive unit assembly 310 and extends downward
through the upper shelf 306. The proximal end of the steel tape
(232 shown in FIGS. 19-20) is engaged with the drum housed within
the drive unit assembly 310, while the distal end of the steel tape
232 is coupled with the target pickup apparatus 220 as shown in
FIGS. 19-20. The drive assembly 310 has: (i) a first one-way clutch
and gear assembly 311 that is engaged with the drum, (ii) a second
one-way clutch and gear assembly 312 that is controllably engagable
with the steel tape extending therethrough, and (iii) a drive motor
313 that cooperates with a chain (not shown) to provide a driving
force to the first one-way clutch and gear assembly 311 and the
second one-way clutch and gear assembly 312.
[0074] Accordingly, the pickup head device 223 of the target pickup
apparatus 220 extends downward with the target leading tube 315
when not in use. A gate valve assembly 325 is mounted onto a port
in the hot cell directly underneath the target leading tube 315.
The gate valve assembly 325 has a flange 327 for engaging a
transfer tube (shown as item 267 in FIG. 24) that is operably
interconnected with a target station 250 (FIG. 24). The gate valve
(not shown) within gate valve assembly 325 is opened and closed by
an actuator 326. Mounted onto the lower shelf 307 are carriage
rails 340 on which is conveyed backward and forward a docking
station carriage table 328. A docking station 330 is mounted onto
the docking station carriage table 328. The docking stations is
also precisely positionable sideways by a pair of linear
translators 341. The docking station 330 comprises a housing having
four linearly aligned bores 332, 334, 336, 338. Bore 332 is a
through hole connecting target leading tube 315 and the top of the
gate valve assembly 325. Bore 334 is provided to receive and store
the target capsule apparatus pusher 225 component of the target
pickup apparatus 220, when it is not in use. Bore 336 is provided
to receive an assembled target capsule assembly 200 with its
proximal end 212 in an upward position. Bore 338 is provided to
receive an irradiated target capsule assembly 200 for dissolution
therein of the molybdate ions and pertechnetate ions from the
irradiated circular target plate 140.
[0075] In use, within a hot cell using remote-controlled devices
(not shown), a Mo-100-coated target plate 140 is mounted into a
target capsule assembly 200. The loaded target capsule assembly 200
is placed by the remote-controlled devices into target capsule
assembly receiving bore 336 while docking station carriage table
328 is positioned by remote control forward and clear of upper
shelf 306. Docking station carriage table 328 is then driven by
remote control to a position under upper shelf 306 such that
linearly aligned bores 332, 334, 336, 338 are centrally aligned
with the gate valve assembly 325. The docking station 330 is then
conveyed sideways to precisely position bore 336 underneath the
target leading tube 315 thus being simultaneously positioned above
gate valve assembly 325. The transfer drive unit assembly 310 is
then operated to deploy sufficient steel tape to engage the target
pickup apparatus 220 with the target capsule apparatus 200, and
then, the transfer drive unit assembly 310 is reversed to draw the
target capsule apparatus 200 up into target leading tube 315. The
docking station 330 is moved to align bore 332 with the target
leading tube 315 thus being simultaneously directly above gate
valve assembly 325, after which actuator 326 is operated to open
the gate valve. Release actuator 319 is operated to release the
target capsule apparatus 200 from the target pickup apparatus 220
thereby allowing the target capsule apparatus 200 to fall through
the bore of gate valve assembly 325 and into transfer tube 267.
Then, docking station 330 is moved so that target capsule pusher
receiving bore 334 is directly under the target leading tube 315.
The transfer drive 310 is operated to engage the target pickup
mechanism 220 with the target capsule apparatus pusher 225 by
deploying steel tape from the drum within the transfer drive unit
310 by the pinch rollers 318 in cooperation with the pinch roller
linear actuator 316, the pinch roller cam linkage 317 and the
second one-way clutch and gear assembly 312 (first one-way clutch
and gear assembly 311 operating freely (i.e. not transferring
force), so that prongs 224 in the pickup head device 223 of the
target pickup apparatus 220 engage the target capsule apparatus
pusher 225. The target pickup apparatus 220 engaged with the pusher
225 is then drawn up into target leading tube 315 by first
disengaging pinch rollers 318 by operating the pinch roller linear
actuator 316 in cooperation with the pinch roller cam linkage 317,
and then re-winding the steel tape onto the drum of transfer drive
apparatus 310 with the first one-way clutch and gear assembly 311
in cooperation with the drive motor 313 (the second one-way clutch
and gear assembly 312 operating freely (i.e. not transferring
force). The docking station 330 is then moved so that bore 332 is
directly under the target leading tube 95. The transfer drive
apparatus 315 is then operated to deploy the steel tape by the
pinch rollers 318 in cooperation with the pinch roller linear
actuator 316, the cam linkage 317, and the second one-way clutch
312 (first one-way clutch and gear assembly 311 operating freely
(i.e. not transferring force) so that the target pickup apparatus
220 with the pusher 225 pushes the target capsule assembly 200
through the transfer tube 267 to deliver the target capsule
assembly 200 to a target station assembly (shown as 270 in FIGS.
24-27) that is operably coupled to a cyclotron.
[0076] FIGS. 24-27 show a target station assembly 250 comprising an
exemplary target station housing 252 for receiving a target capsule
apparatus 200 delivered by a target pickup apparatus 220, wherein
the target capsule apparatus 200 will then be mounted into a loaded
position in the target station housing 252 (FIG. 27). The target
station assembly 250 is mounted onto a PETtrace.RTM. cyclotron (not
shown) by framework 251. The target station housing 252 is engaged
to a cylindrical support element 256 to which is interconnected a
first pneumatic drive cylinder 270. The target station housing 252
comprises a receiving chamber 253 (best seen in FIG. 27) and an
irradiation chamber 254 (best seen in FIG. 26) provided with a port
259 for engaging a cyclotron proton emission port (not shown). The
receiving chamber 253 is connected to a transfer tube 267 through
which a target capsule apparatus 200 is delivered by a target
pickup apparatus 220. The target capsule apparatus 200 is moved
within target station housing 252 from the receiving chamber 253 to
the irradiation chamber 254 by a target holder device 255
interconnected with a second pneumatic drive cylinder 272. Target
holder device 255 is operably connected with limit switches 262
(FIG. 25) for remote sensing of the target capsule apparatus 200.
Once the target capsule apparatus 200 is in the irradiation chamber
254, it is sealingly engaged with the target housing front flange
261 by the first pneumatic drive cylinder 270. The cylindrical
support element target 256 comprises a cooling tube assembly 257
that is moved by the first pneumatic drive cylinder into the target
capsule apparatus 220 once it has been installed in the irradiation
chamber 254 and simultaneously pushes the target capsule apparatus
against the target housing front flange 261 forming a vacuum tight
seal. Accordingly port 259 is sealingly engaged with the cyclotron
thus forming a contiguous vacuum chamber with the cyclotron and
allowing the free passage of energetic protons to the target plate
140/199. The cooling tube assembly 257 engages with the cooling
distribution sleeve 215 of the target capsule assembly to deliver
cooling fluid through passages 218. After its installation into the
target station irradiation chamber 254, the loaded target capsule
assembly 200 is now ready for proton irradiation. After proton
irradiation is complete, the cooling fluid is purged from the
cooling tube assembly 257 and the cooling tube assembly withdrawn
from the cooling distribution sleeve 215 by the first pneumatic
drive cylinder 270. The irradiated target capsule assembly 200 is
removed from the irradiation chamber 254 to the receiving chamber
253 of the target station housing 252 by operation of the second
pneumatic drive cylinder 272. The irradiated target capsule
assembly 200 is then recovered from the target station assembly 250
by engaging the pickup head device 223 of target pickup apparatus
220 with the chamber 212 in the proximal end of the target capsule
assembly 200 in cooperation with the landing pad apparatus 258 and
limit switches 262. The target capsule assembly 200 is then
delivered back to the receiving cell apparatus 300 by recovery of
the deployed steel tape 232 onto the drum provided in the drive
unit assembly 310 by engagement of the first one-way clutch and
gear assembly 311, until the target capsule unit 200 egresses from
the transfer tube 267 and out of the gate valve assembly 325. The
docking station 330 is then conveyed to position target plate
dissolution module 338 precisely underneath the target leading tube
315. The drive unit assembly 310 is then operated to press target
capsule assembly 200 into the dissolution module 338 thereby
forming a liquid tight seal between the target plate 140/199 and
the dissolution module 338. As will be described in more detail
later, the pertechnetate ions and molybdenate ions are then
dissolved from the irradiated target plate, recovered and then
separately purified.
[0077] Due to facility design and space organization limitations,
some cyclotron facilities may require locating a hot cell wherein
is installed an exemplary receiving cell apparatus according to the
present disclosure, at some distance from the target station
assembly mounted onto a cyclotron to which the receiving cell
apparatus is connected by a transfer tube. As the length of the
transfer tube and the number of bends that are required to navigate
the distance between a receiving cell apparatus and a target
station assembly, increase, so increases the stress and strain on
the drive unit assembly and steel tape components of the receiving
cell apparatus used to deliver and recover target capsule
assemblies to and from the target station assembly. Accordingly,
another embodiment of the present disclosure pertains to booster
station apparatus that can be installed into a transfer tube
interposed the receiving cell apparatus and the target station
assembly. An exemplary booster station apparatus 400 is shown in
FIGS. 28, 29A, 29B, and generally comprises a booster station
framework 415 and a booster station housing 410. The booster
station framework 415 comprises a transfer tube support plate 425
having an orifice through which a first transfer tube (not shown)
is inserted, a booster housing back plate 420 and a framework
stabilizing plate 427 having one end engaged with the transfer tube
support plate 425 and the other end engaged with the booster
housing back plate 420. The booster station apparatus is provided
with a flange 422 (best seen in FIG. 29B) provided with an orifice
for engaging the end of the first transfer tube. The housing 410 is
provided with an orifice 412 aligned with the orifice of the flange
430 and flange 422. The orifice 412 in housing 410 allows insertion
of a second transfer tube (not shown). The second transfer tube is
engaged in the orifice of flange 430. A pinch roller assembly
comprising an extendible/retractable framework comprising a pair of
upper pivotable mount assemblies 445 unto which is mounted an upper
roller 440, a pair of lower pivotable mount assemblies 455 unto
which is mounted a lower roller 450, and flange 430 connecting a
left-hand pair of an upper pivotable mount assembly and a lower
pivotable mount assembly (both shown as 445, 455) with the
corresponding right-hand pair (not shown) of an upper pivotable
mount assembly and a lower pivotable mount assembly. A pair of
actuators 460 for extending and retracting the pinch roller
assembly 445,455, 430 is mounted onto the booster station framework
415. A drive unit 465 is mounted onto the pinch roller assembly
445,455, 430 for rotating the upper roller 440 when the pinch
roller assembly 445,455, 430 is extended. When the pinch roller
assembly 445,455, 430 is in a retracted position as shown in FIG.
29A, the upper roller 440 and the lower roller 450 are positioned
further apart than the diameter of the target tube to allow a
target capsule apparatus and target pickup apparatus to pass
through the booster station. When the pinch roller assembly
445,455, 430 is fully extended as shown in FIG. 29B, the upper
roller 440 and lower roller 450 frictionally engage the upper and
lower surfaces of the steel tape to deliver a motive force provided
by the drive unit 465 to assist delivery of the target capsule
apparatus to the target station assembly engaged with the cyclotron
or to assist delivery of the target capsule apparatus to the
receive cell depending on the direction of rotation of drive unit
465. The degree of friction provided is regulated by the pneumatic
pressure delivered to linear actuators 460.
[0078] Another exemplary aspect of this embodiment of the present
disclosure relates to a process for the dissolution of and recovery
of molybdate ions and pertechnetate ions from proton-irradiated
target plates, followed by separation of and separate purification
of the molybdate ions and pertechnetate ions. The exposed surfaces
of a proton-irradiated target plate is contacted with a
recirculating solution of about 3% to about 30% H.sub.2O.sub.2 for
about 2 min to about 30 min to dissolve the molybdate ions and
pertechnetate ions from the surface of the target plate thereby
forming an oxide solution. The peroxide solution may be
recirculated. The peroxide solution may be heated, for example, by
heating the dissolution chamber 338 with heater cartridges placed
in the body of the chamber. The oxide solution is recovered after
which, the dissolution system and the target plate are rinsed and
flushed with distilled deionized water. The rinsing/flushing water
is added to and intermixed with the oxide solution. The pH of the
recovered oxide/rinsing solution is then adjusted to about 14 by
the mixing in of about 1N to about 10N of KOH or alternatively,
about 1N to about 10N NaOH, after which, the pH-adjusted
oxide/rinsing solution may be heated to about 80.degree. C. for
about 2 min to about 30 min to degrade any residual H.sub.2O.sub.2
in the pH-adjusted oxide/rinsing solution. The strongly basic pH of
the oxide/rinsing solution maintains the molybdenum and technetium
species as K.sub.2[MoO.sub.4] or Na.sub.2[MoO.sub.4] and
K[TcO.sub.4] or Na[TcO.sub.4] ions respectively, or forms
exemplified by Mo.sub.2(OH)(OOH),
H.sub.2MO.sub.2O.sub.3(O.sub.2).sub.4, H.sub.2MoO.sub.2(O.sub.2),
and the like.
[0079] The pH-adjusted (and optionally heated) oxide/rinsing
solution is then pushed through a solid-phase extraction (SPE)
column loaded with a commercial resin exemplified by DOWEX.RTM.
1.times.8, ABEC-2000, Anilig Tc-02, and the like (DOWEX is a
registered trademark of the Dow Chemical Co., Midland, Mich., USA).
The pertechnetate ions are immobilized onto the resin beads while
molybdate ions in solution pass through and egress the SPE column.
The molybdate ion solution is collected in a reservoir. The SPE
column is then rinsed with a suitable solution so as to maintain
pertechnetate affinity for the SPE column, but to ensure molybdate
and other impurities have been removed. The rinse solution is added
to collected molybdate ion solution. The pertechnetate ions are
then eluted from the SPE column with tetrabutylammonium bromide
(5-10 mL) in CHCl.sub.3 (0.1-1.0 mg/mL). Alternatively, the
pertechnetate ions can be eluted from the SPE column with NaI
(0.1-1.0 mg/mL).
[0080] The pertechnetate ion solution eluted from the SPE column is
pushed through an alumina column preceded by an appropriate column
to remove elution components. For Dowex.RTM./ABEC, the alumina
column is preceded by a cation exchange SPE cartridge to remove
residual base from the eluent. The alumina column can also be
preceded by an SPE cartridge to remove iodide from the eluent,
wherein the pertechnetate is immobilized on the alumina. It is
optional to use NaI to remove TcO.sub.4, in which case, asn Ag/AgCl
SPE cartridge is required in from of the alumina column. The
adsorbed pertechnetate ions are washed with water, and then eluted
with a saline solution comprising 0.9% NaCl (w/v) through a 0.2
micron filter and collected into vials in lead-shielded containers.
The eluant from the alumina column comprises pure and sterile
Na[TcO.sub.4].
[0081] The molybdate ion/rinse water solution collected from the
SPE column is dried. Suitable drying methods are exemplified by
lyophilization. The resulting powder is suspended in a NaOH
solution of about 3% to about 35% or alternatively, a KOH solution
of about 3% to about 35%, after which the solution may be filtered
and dried. The resulting powder is solubilized in distilled water
and dried again to provide a clean Na.sub.2MoO.sub.4 product or
alternatively, a K.sub.2MoO.sub.4 product. The Na.sub.2MoO.sub.4 or
K.sub.2MoO.sub.4 is then pushed through a strongly acidic cation
exchange column to enable recovery and elution of
H.sub.2[MoO.sub.4] and other polymeric oxide species of molybdenum
exemplified by heptamolybdate, octamolybdate. The eluted molybdate
oxides are then frozen, dried and stored. The dried molybdate oxide
powders thus recovered and stored can be reduced as described above
for coating onto fresh target plates.
[0082] Accordingly, another exemplary embodiment of the present
disclosure pertains to systems and apparatus, also collectively
referred to as dissolution/purification modules, that are engagable
and cooperable with the exemplary receiving cell apparatus
disclosed herein, for receiving and mounting therein irradiated
Mo-100-coated target plates for dissolution, recovery and
purification of molybdate ions and pertehnetate ions. The exemplary
dissolution/purification modules of this embodiment of the
disclosure generally comprise:
[0083] (i) a sealable container for remotely mounting therein an
irradiated Mo-100-coated target plate (referred to as the
"dissolution chamber");
[0084] (ii) a recirculating supply of an H.sub.2O.sub.2 solution
comprising a reservoir, a conduit infrastructure interconnecting
the reservoir and the dissolution container, pumps for
recirculating the H.sub.2O.sub.2 solution, ingress ports for
providing inputs of fresh H.sub.2O.sub.2 solution, egress ports for
controllably removing portions of the recirculating H.sub.2O.sub.2
solution, and instrumentation for monitoring radioactivity,
temperature, flow rates and the like in the recirculating
H.sub.2O.sub.2 solution;
[0085] (iii) a supply of distilled water interconnected with the
dissolution container for post-dissolution washing of the
dissolution container and the recirculating supply of the
H.sub.2O.sub.2 solution;
[0086] (iv) a chemical processing station comprising a plurality of
ports for individually engaging therewith disposable resin
cartridges for immobilizing thereon and mobilizing therefrom
pertechnetate ions and molybdate ions, a conduit infrastructure for
separately recovering pertechnetate ions, molybdate ions, and waste
washings from the resin cartridges, and a filling/capping station
for capturing and storing the recovered pertechnetate ions,
molybdate ions, and waste washings.
* * * * *