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Transcript of Radiopharmaceutical Production Radionuclide Production Practical Targets Design and Construction...
Radiopharmaceutical Production
Radionuclide Production
Practical Targets
Design and Construction
STOP
Requirements in Targetry • Need to produce radionuclides reliably to
meet our research needs• Need to produce large quantities to meet
current and future demands• May need high specific activity for
diagnostic or research applications• Simple targets which do not degrade in
performance• Recycle enriched isotopes• Minimize the amount of non-radioactive
isotope in the final product (high specific activity)
• Targets which will withstand high power deposition and use favorable nuclear reactions
Contents• Basic Principles• Carbon-11 Example• Fluorine-18 example• Iodine-124 example• Summary
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Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Basic Principles
Choice of Nuclear Reaction Choice of the physical state
Gas target Water target Solid target
Choice of processing Gas target - chemical
separation Solid target - distillation
or sublimation Choice of the chemical form
Element or Compound
Target Geometry What is the best shape
for the target Target Body Material
Chemical Interactions Thermal Conductivity Activation
Front Foil Material Strength Chemical Interactions
There are several decisions which must be made when starting to design a cyclotron target. These include:
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Carbon-11 20.4 min
Fluorine-18 110 min
Nitrogen-13 10 min
Oxygen-15 2 min
Isotope half-life
As an example, let us assume we want to produce carbon-11. There are several potential nuclear reactions which may be used to produce C-11.
The possibilities are given in the following slides
Carbon-11 Example
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Potential Reactions
We can explore the potential nuclear reaction pathways by looking at a chart of the nuclides. We want all the reactions to end on carbon-11, but they can start from different stable elements (black squares)
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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Types of Nuclear Reactions
3He, nα,2n
α,n
p,3n p,2n p,n p, γd,n
p,pn Target d,p
p, α p,2pNuc
lear
Cha
rge
Nuclear Mass
The radionuclides that can potentially be made from different nuclear reactions are shown in the following diagram. The first letter is the particle in and the letter after the comma is the particle(s) emitted by the excited nucleus. This template can be overlaid on a chart of the nuclides to get the products
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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Potential Reactions
11B(p,n)11C
Proton inNeutron out
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Potential Reactions
14N(p,α)11C
Proton in
Alpha particle out
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Potential Reactions
12C(p,pn)11C
Proton in
Proton and Neutron out
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Carbon-11 Production
Production Routes
0.0
50.0
100.0
150.0
200.0
250.0
300.0
350.0
400.0
450.0
500.0
0 5 10 15 20 25 30 35
Energy (MeV)
Cro
ss s
ecti
on
(m
b)
11B(p,n)11C
14N(p,a)11C
12C(p,pn)11C
• Three potential nuclear reactions
– 14N(p,α)11C– 11B(p,n)11C– 12C(p,pn)11C
The cross sections for these three reactions are given in the table below
In terms of the yield of the nuclear reactions, it is clear that the best choice is the 11B(p,n)11C reaction
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
PET Radioisotope Production
• One must choose the chemical form for the target. The best choice is a Solid Phase Target
• The target is boron oxide which is a solid• The 11B(p,n)11C reaction in a boron oxide matrix will produce
carbon dioxide• An example of a target designed for this reaction is shown on
the next slide
The difficulty with these type of solid targets is removing the carbon-11 carbon dioxide efficiently from the boron oxide matrix
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
protons
Helium in
11COx in Helium out to flow-throughchemistry
11B + 11B216O3
11COx flow-through target
Target design features
Use of B2O3 to provide oxygen for COx production
Enriched 11B to increase yield
Slanted target material to increase 11COx diffusion
High temperature to increase 11COx diffusion
Helium carrier gas to remove 11COx from target
The actual yields are quite low due to the difficulty of getting the 11CO2 out
John Clark - circa1975
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Carbon-11 ProductionThe next option to be considered is the Nitrogen Gas Target for 14N(p,α)11C reaction. This target has the advantage of using a gas as the target material which makes the extraction of the carbon-11 carbon dioxide much easier.
Gas target body is made from polished aluminum
Gas inlet
Gas outletWater cooling channels
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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Carbon-11 ProductionThis is a cutaway drawing of a typical target for the production of carbon-11 from nitrogen-14 in the chemical form of nitrogen gas.
Nitrogen Gas Target for 14N(p,α)11C reaction
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Range of protons in N2 Gas at 1 atm
Energy Range (MeV)4.50 277.00 mm5.00 332.37 mm5.50 392.20 mm6.00 456.41 mm6.50 524.95 mm7.00 597.76 mm8.00 755.83 mm9.00 930.42 mm10.00 1.12 m11.00 1.33 m12.00 1.55 m13.00 1.79 m14.00 2.04 m15.00 2.31 m16.00 2.59 m
The first decision is how long to make the target and what pressure to use. If we want to stop the beam we can calculate the range of the protons in the gas. At 1 atmosphere, the target would need to be 2.6 meters long to stop the beam.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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Range of protons in N2 Gas at 10 atm
Energy Range (MeV)4.00 22.62 mm4.50 27.70 mm5.00 33.24 mm5.50 39.22 mm6.00 45.64 mm6.50 52.50 mm7.00 59.78 mm8.00 75.58 mm9.00 93.04 mm10.00 112.12 mm11.00 132.79 mm12.00 155.03 mm13.00 178.81 mm14.00 204.12 mm15.00 230.92 mm16.00 259.21 mm
At a pressure of 10 atmospheres, the beam will stop in about 26 cm. Which is a much more reasonable target length although most nitrogen targets are shorter than this and operate at higher pressures.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Shape of the Target
Energy Straggling (MeV)4.00 730.98 um4.50 885.82 um5.00 1.05 mm5.50 1.23 mm6.00 1.42 mm6.50 1.63 mm7.00 1.84 mm8.00 2.31 mm9.00 2.82 mm10.00 3.37 mm11.00 3.97 mm12.00 4.61 mm13.00 5.29 mm14.00 6.01 mm15.00 6.78 mm16.00 7.58 mm
8.0 mm
We need to decide the shape of the target. We know that the beam will spread out due to small angle multiple scattering. This straggling can be calculated most easily using a program such as SRIM
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Entrance Foil Material
Material density(g/cm3)
Melt. Pt.(°C)
Tensile St.
(kpsi)
Thermal Cond.
(watt/cm-°K)
dE/dx(MeV/g/cm2)
Carbon 2.2 >3000 --- 2.51 41.08
Aluminium
2.71 660 30 2.37 33.96
Titanium 4.5 1668 120 0.31 29.77
316Stainless
8.02 1427 120 0.29 28.91
Havar 8.3 1493 250 0.17 28.6
Nickel 8.9 1453 120 0.91 28.53
Tantalum 16.6 2996 70 0.53 18.57
Tungsten 19.3 3387 500 1.8 18.42
Platinum 21.4 1769 20 0.72 18.3
Niobium 8.57 2477 40 0.54
The table below gives the physical characteristics of some common foil materials. The ideal has high strength, low density, good thermal conductivity, a reasonable dE/dx and high melting point. None is perfect but Al, Ti and Havar are common.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Getting High Specific ActivityIn order to get high specific activity carbon-11, it is necessary to
take precautions when fabricating the target. These include:
• Use Electrical Discharge machining to cut the metal
• Use only alumina (Al2O3) abrasives in polishing the inside surface.
• Never use oils in the target• If organic solvents must be used, follow the use with repeated
rinses of ethanol and water
Cleaning the target• Should never need to be cleaned• If it is necessary, then Acetone and Ethanol should be used as
they are soluble in water• If abrasives are used, they should be alumina • The target should be irradiated and the gas discarded after any
cleaning procedure and before a production irradiation
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Carbon-11 20.4 min
Fluorine-18 110 min
Nitrogen-13 10 min
Oxygen-15 2 min
Isotope half-life
Fluorine-18 Example
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Fluorine-18 Example
Proton inNeutron out
There is really only one reasonable nuclear reaction with protons as the bombarding particle. This is the 18O(p,n)18F reaction.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
18O(p,n)18F Reaction
The nuclear reaction cross section is shown on the right and it should be noted that the peak of the reaction is about 6 MeV and it tails off rapidly above 11 MeV.
The most convenient chemical form of the target material is in the form of oxygen-18 enriched water. This is the reaction that is used by nearly all facilities for the production of FDG
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Fluorine-18 Fluoride Production
• The target is usually a depression cut into a metal block which contains the oxygen-18 enriched water
• There is a inlet and outlet for the water and the target is deep enough to allow some boiling in the target without loosing yield.
• The rear of the target is cooled with a high pressure water flow
• The front foil is made of a material that is strong enough to hold the pressure generated by the boiling water and chemically resistant to the fluoride and the oxygenated species like peroxide generated in the water.
Beam
Cooling water
Target waterFront flange
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Fluorine-18 Fluoride Production
Typical water target. This particular target is made from solid silver to help in the heat transfer. A more modern water target is typically made from niobium.
• 18O(p,n)18F Nuclear Reaction in 95% enriched water• Volume of the target from 0.3 mL up to 3.0 mL
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Water Target Operation
Beam
Helium push gas
Vent
To the Chemistry Lab
[18O]Water
Filling and Irradiation Cycle
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Water Target Operation
Beam
Helium push gas
Vent
To the Chemistry Lab
[18O]Water
After Irradiation, pushing the water from the target to the Chemistry Lab
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
F-18 transfer line - 60 meters
Transfer of the F-18 from the Cyclotron to the Chemistry
Laboratory
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Initial Fabrication and Cleaning of F-18 targets
Fabrication of Fluorine targets• Should never use soldering fluxes as they contain fluorine which
will reduce specific activity• The back wall should be thin to allow good heat transfer• A “reflux” volume helps with keeping the target material in the
liquid state
Cleaning of Fluorine targets• Silver targets need to be cleaned fairly frequently• Niobium and Titanium can be cleaned much less frequently• No cleaning may be necessary if these last two are used• Mild abrasive and repeated water rinses are best
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Iodine-124 ExampleAs the next example, suppose you wanted to make I-124 on the cyclotron and wanted to design a target for the production
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Chart of the Nuclides
n
p
Here we can use the 124Te(p,n)124I nuclear reaction
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Cross-section 124Te(p,n)124IThis excitation function for the nuclear reaction shows that the best energy interval is from 15 down to about 5 MeV
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Tellurium Solid TargetsHere we have the option of two different chemical forms of the tellurium to use for the target. We can use tellurium metal as shown on the left or tellurium dioxide as shown on the right
Both of these target materials are used for production and the choice depends on ease of chemical processing and target material recovery. Since the target material is isotopically enriched, it is relatively expensive and so must be recovered
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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Preparation of solid targets by electrodeposition
· Requirements· The layer must be homogeneous over the entire surface
area to ±5%.· The layer must adhere strongly to the carrier up to the
irradiation temperatures.· The layer must be smooth (not spongy), dense (no
occlusions nor vacuoles), and stress free.· The layer must be free of any organic plating additives
(complexing agents or surfactants).
The tellurium metal target may be prepared by electrodeposition. There are several constraints on the targets prepared this way. Some of these are given below.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Electrodeposition Apparatus
• A diagram of an electrodeposition apparatus is shown on the right
• This particular apparatus will prepare four targets simultaneously.
• The composition of the solutions used to prepare these targets are beyond the scope of this presentation, but may be found in the IAEA publication TRS 432
• A picture of the actual apparatus is shown on the next slide.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Electrodeposition Apparatus
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Radioiodine Production• The target can be an internal target which can have a very low
angle of incidence and high power dissipation• The target is mounted inside the vacuum tank of the cyclotron
and is irradiated under high vacuum• Loss of the I-124 during irradiation is a concern
Courtesy of John Clark
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Radioiodine Production• The idea of an inclined plane can be used as well with the target
attached directly to the cyclotron• This target attaches to the beam port of the cyclotron
Courtesy of Advanced Cyclotron Systems, Inc.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Range of Protons in TeO2
Energy Range(MeV)4.50 204.55 um5.00 242.96 um5.50 284.11 um6.00 327.95 um6.50 374.42 um7.00 423.48 um8.00 529.12 um9.00 644.68 um10.00 769.91 um11.00 904.59 um12.00 1.05 mm13.00 1.20 mm14.00 1.36 mm15.00 1.53 mm16.00 1.71 mm17.00 1.90 mm18.00 2.10 mm20.00 2.52 mm
The target can also be formed from a tellurium dioxide powder target. This target has the advantage of being able to be reused without extensive processing by distilling the iodine out of the TeO2.. The target needs to be about 1.5 mm thick
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Depth distribution of 124I yield
0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.600
2
4
6
8
10
12
14
1
24 I
yie
ld p
er
segm
ent,
% o
f to
tal yie
ld
TeO2 target depth, mm
The yield will vary as a function of depth into the target. In this plot we see the yield as a function of depth into the target. You can see that the yield is very low when the beam has penetrated 0.6 mm into the target. This can be compared to the excitation function as shown on the previous slide.
The target is 124TeO2, with a incident proton energy of 14.9 MeV)
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Initial target preparationTo prepare the target, the enriched tellurium dioxide powder is placed in a platinum dish which has a depression of about 1.5 mm deep.
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Inserting the target into furnace
The platinum dish is placed in the furnace to melt the TeO2 powder into a glass for irradiation
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Supercooled liquid TeO2 on the Pt disk
After melting, the powder has formed a glass and is ready for irradiation
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
TeO2 before and after irradiation
• After irradiation with IBA Cyclone 18/9 (20 min, 6 μA, 13,5 MeV protons): yield ~1,5 mCi (56 MBq) 124I
After irradiation
Before irradiation
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Thermochromatographic release of radioiodines
The I-124 is distilled out of the TeO2 target and then the target can be reused
°C
Solution for trapping radioiodine
Air out
Air in
Al2O3 trap for TeO2 vapours
TeO2 target melted on a platinum disk
Heater Thermocouple
Radiopharmaceutical Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Final SummaryHere are the steps we must take to design and build useful targets• Simple targets can be designed, but the material and method of
construction is critical• The physical form of the target material often determine the
recycling• Non-radioactive isotopes have many sourcesHigh power targets are being developed
There are several characteristics of targets which make them more useful and robust
• Simple targets which do not degrade in performance• Recycle enriched isotopes• Minimize the amount of non-radioactive isotope in the final
product• Targets which will withstand high power deposition and use
favorable nuclear reactions
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