Radiopharmaceutical Production

Radiopharmaceutical Production

Radionuclide ProductionPractical Targets

Design and Construction

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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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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:

http://www.iaea.org/index.html


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



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

Potential ReactionsWe 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)



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

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



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

Potential Reactions

11B(p,n)11C

Proton inNeutron out



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

Potential Reactions

14N(p,α)11C

Proton inAlpha particle out



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



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

ectio

n (m

b)

11B(p,n)11C14N(p,a)11C12C(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



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



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



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



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

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



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.



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

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.



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



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 41.08Aluminiu

m2.71 660 30 2.37 33.96

Titanium 4.5 1668 120 0.31 29.77316Stainless

8.02 1427 120 0.29 28.91

Havar 8.3 1493 250 0.17 28.6Nickel 8.9 1453 120 0.91 28.53Tantalum 16.6 2996 70 0.53 18.57

Tungsten 19.3 3387 500 1.8 18.42Platinum 21.4 1769 20 0.72 18.3Niobium 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.



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



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



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.



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



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



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



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



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



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



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



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



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

Chart of the Nuclides

np

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

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



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



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

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.



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.



Practical Targets

Contents

Basic Principles

Carbon-11 Example

Fluorine-18 example

Iodine-124 example

Summary

STOP

Electrodeposition Apparatus



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



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.



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



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

12

4 I yie

ld p

er s

egm

ent,

% o

f tot

al y

ield

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)



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.



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



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



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



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



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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Radiopharmaceutical Production

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