Cyclotron Produced

Radiopharmaceuticals
Contents
o Introduction
o Motion in Magnetic Field
o RF Acceleration
o Ion Source
o Ion Extraction
o Nuclear Reactions
o Radiopharmaceutical Production
 Introduction
Radiopharmaceutical E.O. Lawerence - Father of the Cyclotron
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
 Introduction
Radiopharmaceutical Major Components
Production
• Major components
Cyclotron Basics
– Magnet
Contents – Ion source
Introduction – RF power
Magnetic Field – “dee” structure
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
 Introduction
Radiopharmaceutical
Classical Cyclotron
Production
• D1 and D2 are called dees
because of their shape
Cyclotron Basics
• A high frequency
Contents alternating potential is
Introduction applied to the dees
Magnetic Field • A uniform magnetic field is
RF acceleration perpendicular to them
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
 Motion in a Magnetic Field
Radiopharmaceutical
Production

For a B field in the y direction, a positively charged particle with

Cyclotron Basics
charge q moving with velocity v in the x direction will feel a force
Contents
F = qvB in the z direction
Introduction
Magnetic Field magnitude: Fmagnetic = q v B sin(qvB)
RF acceleration direction:
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
Radiopharmaceutical
Ion Path
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
Radiopharmaceutical
Ion Source
Production • The ions are usually generated in a plasma discharge
• The ion source can be either external or internal
• In most ion sources a gas of neutral atoms or molecules is
Cyclotron Basics
“heated” into a plasma state were ions and electrons are
Contents dissociated and move independently as free particles.
Introduction • The heating mechanism can be of various kinds. It can be
Magnetic Field thermal, electrical, or use laser light.
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
 Central Region Beam Path
Radiopharmaceutical
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

• As the ion exits the ion source the path it takes is determined by
STOP
the environment of the central region.
 Ion Extraction
Radiopharmaceutical
Production
• Once the beam has been accelerated to the desired energy, it
usually must be extracted from the cyclotron in order to
Cyclotron Basics
bombard a target and create the radionuclide.
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

STOP
 Positive Ion Extraction
Radiopharmaceutical
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

The beam is deflected by an electric field out of the cyclotron.

STOP
Radiopharmaceutical
Positive Ion Extraction
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

Deflector with split septum used for positive ion extraction

STOP
 Particle Extraction
Radiopharmaceutical
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

The electrons are stripped off the accelerated ions and this causes
them to be directed out of the cyclotron by the magnetic field acting
STOP
on them.
 Negative Ion Extraction
Radiopharmaceutical
Production

Cyclotron Basics
Contents
Introduction
Magnetic Field
RF acceleration
Ion Source
Ion Injection
Ion Extraction
Beam Transport

Carbon foil used to extract negative ion beam

STOP
 How are radioisotopes made
Radiopharmaceutical
Production
with a particle accelerator
The goal of cyclotron targetry is to produce a radionuclide. To do
Cyclotron Targetry
Overview
this one must get the target material into the beam, keep it there
during the irradiation and to remove the product radionuclide from
Contents the target material quickly and efficiently. The specific design of
General Principles the target is what allows one to achieve this goal.
Nuclear reactions and
target physics An accelerator shoots
Beam heating and a particle at high energy
Density reduction +
+
Target Foils
Practical Target design +

The particle reacts with a nucleus to

form a new radioisotope

STOP
 How are radioisotopes made
Radiopharmaceutical
Production
with a particle accelerator
Cyclotron Targetry
Overview

Contents
General Principles
Nuclear reactions and
target physics
Beam heating and
Density reduction
Target Foils
Practical Target design

STOP
 Nuclear Reaction for F-18

❑ Protons are fired at O-18

❑ O-18 absorbs the proton
▪ Temporary creation of F-19
▪ Emission of neutron

❑ Creation of F-18
 Production methods of clinically useful
positron-emitting radio nuclides

The medical cyclotrons are usually located near the PET imager because of
the short half-lives of the radionuclides produced. Fluorine-I8 (F-I8) is an
exception to this generalization because of its longer half-life (110 minutes).
 Nuclear Reaction Cross Sections
Radiopharmaceutical The particle which hits the nucleus can
Production interact in several ways

• Nuclear elastic ELASTIC

Cyclotron Targetry a + A SCATTERING
Overview scattering
• Nuclear inelastic
Contents
scattering with or
General Principles
without nucleon INELASTIC
Nuclear reactions and
emission a + A SCATTERING
target physics
Beam heating and
Aaa
Density reduction
Target Foils
Practical Target design • Projectile b + NUCLEAR
B REACTION 1
absorption with or
without nucleon
emission.

b + c + D NUCLEAR
REACTION 2

STOP Each of these processes has a certain probability of occurring

 Rate of Radionuclide Production
Radiopharmaceutical
Production
In the simplest case, where the cross-section is assumed
Cyclotron Targetry to be constant, the rate of production is given by:
Overview

Contents
General Principles
Nuclear reactions and
target physics The cross-section is always a function of energy. If we use
Beam heating and this more exact expression, then the equation becomes:
Density reduction
Target Foils
Practical Target design

STOP
 Nuclear Reaction Cross Sections
Radiopharmaceutical
Production

Cyclotron Targetry
Overview

Contents
General Principles
Nuclear reactions and
target physics
Beam heating and
Density reduction
Target Foils
Practical Target design

STOP
 Saturation Factor
Radiopharmaceutical
Production

As soon as radioisotopes have been produced, they start

Cyclotron Targetry to decay. This leads to the following expression, where the
Overview
overall rate of production is then:
Contents
General Principles
Nuclear reactions and
target physics
Beam heating and
Density reduction
Target Foils
Practical Target design

STOP
 Yield of Nuclear Reaction
Radiopharmaceutical
Production

Cyclotron Targetry Assuming that the beam current is the same as the particle
Overview flux (which is true only for particles with a charge of +1),
then the yield of a nuclear reaction is given by:
Contents
General Principles
Nuclear reactions and
target physics
Beam heating and
Density reduction
Target Foils
Practical Target design

STOP

Radiopharmaceutical • Besides the chemistry requirements imposed by the post-
Production
Cyclotron Targetry
Overview
Contents
General Principles
Nuclear reactions and
target physics
Beam heating and
Density reduction
Target Foils
Practical Target design
STOP
Physical State of the Target
irradiation need to incorporate the product radionuclide into
particular molecules, other considerations that affect the decision
as to the physical state of the target include the following:
– The atom density of the target species in the target
material—e.g., a solid or liquid might provide higher atom
densities than a gas and thus produce greater amounts of the
desired product.
– The cross section of the intended target atoms for the specific
nuclear reaction of interest—e.g., a small cross section may
require a higher target density, often favoring a solid or liquid
target over a gas.
– The preponderance of interfering species in the irradiated
target—some target materials may contain nuclear species
that produce undesired radioactive products that might be
difficult to separate from the desired species, and such
considerations can affect the type of target selected; similar
considerations may also apply to stable target species that
interfere with separation of the desired product.
– The associated undesired radioactivity of the target materials
following irradiation—high radiation levels of some potential
target materials, as a consequence of incidental irradiation of
miscellaneous species may mitigate against selection of
some target types and/or favor selection of other types.
Radiopharmaceutical
Radionuclide Separation
Production

• After the radioactive product is formed, it must be isolated

Cyclotron Targetry from the residual target material and then chemically
Overview
reacted with appropriate molecules to form the desired
Contents
radiolabeled end-product.
General Principles • Common chemical routes to production of this compound
Nuclear reactions and
involve reactions of fluoride ion, F-, in liquid solutions,
and the use of the liquid target is often reasonable for
target physics
such applications.
Beam heating and
• There are other preparation methods that involve
Density reduction
bubbling fluorine gas (F2) through solutions of appropriate
Target Foils
chemicals. The latter methods might favor use of a
Practical Target design gaseous target from which the 18F2 could be more easily
isolated.

• The choice is governed in part by the reaction yield and

the chemical process that follows.

STOP
 Radiopharmaceutical Productions
• The synthesis of radiolabelled compounds is one of the most critical
aspects of the sequence of events in PET studies.
• The short half-life of the positron emitting radioisotope imposes
some constraints on labelling strategies.
• Radiolabelling of compounds involves considerable amounts of
radioactivity to start with and must be performed by remote control in
lead-shielded hot cells.
Hot Cell
 Airflow
• It is essential that radioactive material
(dust, airborne radioactivity, etc.) is not
drawn from the areas with high levels of
contamination to the areas of low
contamination.
 Radiation Gradient
• With the cyclotron turned off, the highest
level of radiation will be around the
targets.
• The ideal situation is when the facility is
set up in such a way that the staff and
materials follow this gradient and do not
have to pass through a low radiation area
on their way from one high radiation area
to another.
Ideal pressure and radiation gradient
 References
• https://www-pub.iaea.org/MTCD/
Publications/PDF/trs468_web.pdf
• http://www-naweb.iaea.org/napc/iachem
/training-modules/Cyclo_target/Cyclotron%
20Operations/Cyclotron_basics.pptx
• https://inis.iaea.org/collection/NCLCollectionStor
e/_Public/29/016/29016317.pdf
Example of biomedical applications of PET
Radiotracers and radiopharmaceuticals