Practical - Nuclear Sciences and Applications

Report
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
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STOP
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Basic Principles
Radiopharmaceutical
Production
There are several decisions which must be made when
starting to design a cyclotron target. These include:
Practical Targets
Contents
Basic Principles
Carbon-11 Example


Fluorine-18 example
Iodine-124 example
Summary


STOP
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
Carbon-11 Example
Radiopharmaceutical
Production
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.
Practical Targets
Isotope
Contents
half-life
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Carbon-11
20.4 min
Fluorine-18
110 min
Nitrogen-13
10 min
Oxygen-15
2 min
Summary
STOP
The possibilities are given in the following slides
Potential Reactions
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
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)
Types of Nuclear Reactions
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
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
Fluorine-18 example
Iodine-124 example
n
α,n
p,n
p, γ
d,n
p,pn
Target
d,p
3He,
Summary
Nuclear Charge
α,2n
STOP
p,3n
p,2n
p, α
p,2p
Nuclear Mass
Potential Reactions
Radiopharmaceutical
Production
11B(p,n)11C
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Proton in
Neutron out
STOP
Potential Reactions
Radiopharmaceutical
Production
14N(p,α)11C
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Proton in
Alpha particle out
STOP
Potential Reactions
Radiopharmaceutical
Production
12C(p,pn)11C
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Proton in
Summary
Proton and
Neutron out
STOP
Carbon-11 Production
Radiopharmaceutical
Production
The cross sections for these three reactions are given in the table
below
•
Production Routes
Practical Targets
Contents
500.0
Basic Principles
450.0
Carbon-11 Example
400.0
Iodine-124 example
350.0
Summary
Cross section (mb)
Fluorine-18 example
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
300.0
250.0
200.0
150.0
100.0
50.0
0.0
0
5
10
15
20
25
30
35
Energy (MeV)
STOP
In terms of the yield of the nuclear reactions, it is clear that the
best choice is the 11B(p,n)11C reaction
PET Radioisotope Production
Radiopharmaceutical
Production
Practical Targets
Contents
•
•
•
Basic Principles
Carbon-11 Example
Fluorine-18 example
•
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
Iodine-124 example
Summary
STOP
The difficulty with these type of solid targets is removing the
carbon-11 carbon dioxide efficiently from the boron oxide matrix
11CO
x
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
flow-through target
Target design features
Use of B2O3 to provide
oxygen for COx
protons
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
Helium in
11B
+ 11B216O3 11CO in Helium
x
out to flow-through
chemistry
John Clark - circa1975
STOP
Carbon-11 Production
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
The 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 inlet
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Water cooling channels Gas outlet
Gas target body is made from polished aluminum
STOP
Carbon-11 Production
Radiopharmaceutical
Production
This is a cutaway drawing of a typical target for the production
of carbon-11 from nitrogen-14 in the chemical form of nitrogen
gas.
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Nitrogen Gas Target for 14N(p,α)11C reaction
Radiopharmaceutical
Production
Practical Targets
Range of protons in N2 Gas at 1 atm
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.
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Energy
(MeV)
4.50
5.00
5.50
6.00
6.50
7.00
8.00
9.00
10.00
11.00
12.00
13.00
14.00
15.00
16.00
Range
277.00 mm
332.37 mm
392.20 mm
456.41 mm
524.95 mm
597.76 mm
755.83 mm
930.42 mm
1.12 m
1.33 m
1.55 m
1.79 m
2.04 m
2.31 m
2.59 m
Range of protons in N2 Gas at 10 atm
Radiopharmaceutical
Production
At a pressure of 10 atmospheres, the beam will stop in about 26 cm. W
much more reasonable target length although most nitrogen targets are
this and operate at higher pressures.
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Energy
(MeV)
4.00
4.50
5.00
5.50
6.00
6.50
7.00
8.00
9.00
10.00
11.00
12.00
13.00
14.00
15.00
16.00
Range
22.62 mm
27.70 mm
33.24 mm
39.22 mm
45.64 mm
52.50 mm
59.78 mm
75.58 mm
93.04 mm
112.12 mm
132.79 mm
155.03 mm
178.81 mm
204.12 mm
230.92 mm
259.21 mm
Shape of the Target
Radiopharmaceutical
Production
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
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Energy
(MeV)
4.00
4.50
5.00
5.50
6.00
6.50
7.00
8.00
9.00
10.00
11.00
12.00
13.00
14.00
15.00
16.00
Straggling
730.98 um
885.82 um
1.05 mm
1.23 mm
1.42 mm
1.63 mm
1.84 mm
2.31 mm
2.82 mm
3.37 mm
3.97 mm
4.61 mm
5.29 mm
6.01 mm
6.78 mm
7.58 mm
8.0
mm
Entrance Foil Material
Radiopharmaceutical
Production
Practical Targets
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.
Contents
Basic Principles
Material
density Melt. Pt.
(g/cm3) (°C)
Tensile
St.
(kpsi)
Thermal
Cond.
(watt/cm-°K)
dE/dx
(MeV/g/cm2
)
Carbon
2.2
>3000
---
2.51
41.08
Aluminiu
m
2.71
660
30
2.37
33.96
Titanium
4.5
1668
120
0.31
29.77
316
Stainless
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
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Getting High Specific Activity
Radiopharmaceutical
Production
In order to get high specific activity carbon-11, it is necessary to
take precautions when fabricating the target. These include:
Practical Targets
Contents
Basic Principles
Carbon-11 Example
•
•
Fluorine-18 example
Iodine-124 example
Summary
•
•
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
STOP
Fluorine-18 Example
Radiopharmaceutical
Production
Isotope
half-life
Carbon-11
20.4 min
Fluorine-18
110 min
Nitrogen-13
10 min
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Oxygen-15
2 min
Fluorine-18 Example
Radiopharmaceutical
Production
Practical Targets
There is really only one reasonable nuclear reaction with
protons as the bombarding particle. This is the 18O(p,n)18F
reaction.
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Proton in
Neutron out
STOP
18O(p,n)18F
Reaction
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
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
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
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.
Summary
STOP
Fluorine-18 Fluoride Production
Radiopharmaceutical
Production
•
Practical Targets
Contents
Basic Principles
•
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
•
•
STOP
The target is usually a
depression cut into a metal Front flange Target water
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.
Beam
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
Cooling water
fluoride and the oxygenated
species like peroxide
generated in the water.
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
Water Target Operation
Radiopharmaceutical
Production
Filling and Irradiation Cycle
Vent
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Helium push gas
Summary
Beam
[18O]Water
To the Chemistry Lab
STOP
Water Target Operation
Radiopharmaceutical
Production
After Irradiation, pushing the water from the target to the
Chemistry Lab
Vent
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Helium push gas
Summary
Beam
[18O]Water
To the Chemistry Lab
STOP
Radiopharmaceutical
Production
Transfer of the F-18 from the
Cyclotron to the Chemistry
Laboratory
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
F-18 transfer line - 60 meters
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
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
STOP
Iodine-124 Example
Radiopharmaceutical
Production
As the next example, suppose you wanted to make I-124 on the
cyclotron and wanted to design a target for the production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Chart of the Nuclides
Radiopharmaceutical
Production
Here we can use the 124Te(p,n)124I nuclear reaction
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
n
p
STOP
Cross-section 124Te(p,n)124I
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
This excitation function for the nuclear reaction shows that the best
energy interval is from 15 down to about 5 MeV
Tellurium Solid Targets
Radiopharmaceutical
Production
Practical Targets
Here 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
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
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
Preparation of solid targets by
electrodeposition
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
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.
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP

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).
Electrodeposition Apparatus
Radiopharmaceutical
Production
Practical Targets
•
Contents
Basic Principles
Carbon-11 Example
•
Fluorine-18 example
Iodine-124 example
Summary
•
•
STOP
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.
Electrodeposition Apparatus
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Radioiodine Production
Radiopharmaceutical
Production
Practical Targets
Contents
•
•
Basic Principles
Carbon-11 Example
•
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
Fluorine-18 example
Iodine-124 example
Summary
STOP
Courtesy of John Clark
Radioiodine Production
Radiopharmaceutical
Production
Practical Targets
Contents
•
•
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
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Courtesy of Advanced Cyclotron Systems, Inc.
Range of Protons in TeO2
Radiopharmaceutical
Production
Practical Targets
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
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
Energy
(MeV)
4.50
5.00
5.50
6.00
6.50
7.00
8.00
9.00
10.00
11.00
12.00
13.00
14.00
15.00
16.00
17.00
18.00
20.00
Range
204.55 um
242.96 um
284.11 um
327.95 um
374.42 um
423.48 um
529.12 um
644.68 um
769.91 um
904.59 um
1.05 mm
1.20 mm
1.36 mm
1.53 mm
1.71 mm
1.90 mm
2.10 mm
2.52 mm
Depth distribution of 124I yield
Radiopharmaceutical
Production
Practical Targets
Contents
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.
Basic Principles
14
Carbon-11 Example
Iodine-124 example
12
10
8
6
4
2
124
Summary
I yield per segment, % of total yield
Fluorine-18 example
0
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
TeO2 target depth, mm
STOP
The target is 124TeO2, with a incident proton energy of 14.9 MeV)
Initial target preparation
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
To prepare the target, the enriched tellurium dioxide
powder is placed in a platinum dish which has a
depression of about 1.5 mm deep.
Inserting the target into furnace
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
STOP
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
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
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
After irradiation
Before irradiation
STOP
Thermochromatographic
release of radioiodines
Radiopharmaceutical
Production
°C
Heater
Thermocouple
Practical Targets
Contents
Basic Principles
Air in
Carbon-11 Example
Fluorine-18 example
Iodine-124 example
Summary
Air out
Solution for
trapping
radioiodine
STOP
TeO2 target melted on a
platinum disk
Al2O3 trap for TeO2 vapours
The I-124 is distilled out of the TeO2 target
and then the target can be reused
Final Summary
Radiopharmaceutical
Production
Practical Targets
Contents
Basic Principles
Carbon-11 Example
Fluorine-18 example
Here 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 sources
High power targets are being developed
Iodine-124 example
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
Summary
STOP
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