National Medical Cyclotron

What is a cyclotron?
A cyclotron is an electrically powered machine that accelerates
charged particles to high speeds and beams them at a suitable
target, producing a nuclear reaction that creates a radioisotope.
Cyclotrons do not use uranium or produce difficult to dispose of fission product
wastes. When operating, the cyclotron is surrounded by an intense field of
radiation, but this disappears quickly when the machine is switched off. To protect
the operators and the environment, ANSTOs National Medical Cyclotron is housed
in a massive concrete vault with 2.3 metre thick walls.
Cyclotrons belong to a class of machines called particle accelerators. These exist
in two varieties, linear and cyclic. Both create charged particles and accelerate them
to high velocities to bombard target materials. Linear particle accelerators work, as
the name suggests, by accelerating particles in a straight line. Cyclic particle accelerators,
such as the cyclotron, make the particles travel many times around a central point,
thus achieving higher acceleration than is possible with linear accelerators.

The Australian Nuclear Science and Technology Organisation (ANSTO) is

Australias national nuclear research and development organisation and the
centre of Australian nuclear expertise.
ANSTO delivers specialised advice, scientific services and products to
government, industry, academia and other research organisations.
ANSTOs vision is to benefit all Australians and the international community
through the innovative applications of nuclear science and technology and
for ANSTO to be recognised as a leader in selected fields of expertise.

How a cyclotron works

Charged particles (ions) created from a suitable source
material are injected into the centre of the cyclotron. The ions
are then forced to travel in a circular path around a central
point and repeatedly accelerated by electrical fields.
During acceleration, the charged ions are forced by a strong magnetic field to
travel in an outward spiral path, in an evacuated gap between magnetic poles. As
the speed of the particle beam increases, the spiral path of the particles increases
in radius until, when the desired speed is reached, the beam is extracted from the
machine at the ion extraction point.
The extracted beam is guided by magnets to one of several possible targets.
A proton is a particle in the nucleus

When the target is bombarded by the beam of particles, a nuclear reaction occurs,

of an atom weighing about the same

altering the physical composition of the target material and producing radioactivity.

as a neutron but carrying a positive

When, for example, nitrogen gas is used as a target, it is converted into

charge. A neutron carries no charge.

radioactive carbon. Commercial medical cyclotrons are predominantly designed

to produce a beam of protons.

Cyclotron-produced radioisotopes
Cyclotron-produced radioisotopes are used mainly to make radiopharmaceuticals
for use in two diagnostic imaging systems positron emission topography (PET)
and single photon emission computed tomography (SPECT).
Both methods involve the use of minute quantities of low-level radioactive
chemicals that can be detected by the highly sensitive imaging equipment in
hospitals. The radioactive materials decay rapidly and do not harm the patient.
SPECT is a sophisticated camera system that produces images of slices of the
body by photographing the low-energy gamma rays emitted from radioactive
tracers introduced to pinpoint disease or organ function. The radioactive tracers
used contain a radioisotope compound that is specific for the organ or disease
being studied. If the body slices are added together, a three-dimensional image
of the organ being studied is obtained.
SPECT radiopharmaceuticals produced at the National Medical Cyclotron include:

gallium-67, which is used to diagnose soft tissue tumours and some

inflammatory lesions. It has a half-life of 78 hours

thallium-201, which is used to assess heart conditions. It has a half-life of 73 hours

iodine-123, which is used to diagnose certain thyroid diseases. It has a

half-life of 13 hours. Iodine-123 labelled tracers are also commonly used to
monitor neurodegenerative diseases and cancer.

PET is a highly sensitive system that uses positron-emitting radioisotopes.

A positron is a positively charged electron particle. When a positron collides
with an electron the two particles annihilate one another, releasing energy as
two gamma rays which shoot off in exactly opposite directions. These two rays
strike crystals in a ring of detectors around a patient, enabling sophisticated
computers to then turn the information into an image.
The only PET radiopharmaceutical currently routinely produced at the National
Medical Cyclotron is fluorine-18. This is labelled onto a glucose molecule to form
fluorodeoxyglucose (FDG). This is used to diagnose brain disease, heart viability,
coronary artery disease and, increasingly, to assess the spread of cancers such
as malignant melanomas. It has a half-life of 110 minutes.

ANSTOs cyclotron produces

radiopharmaceuticals
used to diagnose
heart conditions,
neurodegenerative
and thyroid diseases,
and cancer.

Clinical applications of cyclotron radioisotopes

Thallium-201, which is produced as thallous chloride, was first used in nuclear
medicine in the mid 1970s. Thallous chloride is a radioactive mimic of potassium,
which means it accumulates in smooth muscle such as the heart, as potassium
does. This makes it especially useful for assessing the firmness of the heart,
because it can be used to produce an image that shows which muscles are
working efficiently and receiving a normal blood flow. If the blood supply is
restricted because the arteries are clogged, it may be possible to treat the problem
through surgery (a coronary bypass) or with drugs. Thallium scans are important
because they reveal the extent of the problem, enabling doctors to decide what
type of treatment is appropriate.
Radioactive iodine is used in nuclear medicine mainly to diagnose and treat thyroid
disorders. Iodine-131, which is produced in a nuclear reactor, is very good for
treatment because it provides a high radiation dose. For most diagnostic work,
a low dose radioisotope such as the cyclotron-produced iodine-123 is used. This
can be safely injected in larger quantities because of its low radiation dose, and
has ideal energies of gamma emission for imaging.
Some of the diagnostic work using iodine-123 involves detecting metastatic, or
secondary, thyroid cancers, often found in bones, the lungs, chest or abdomen.
Where the secondary disease sites consist of thyroid-like cells, they quickly take
up iodine, thus providing a very sensitive indicator of cancer spread.

A tracer is a chemical compound which, when injected, will accumulate in a

specific organ or tumour. A radioactive label is a radioisotope which can be
chemically incorporated into the tracer so that the tracers movement in the
body can be determined using a gamma camera. For example, iodine-123
is used as a radioactive label for several tracers. It is used in diagnostic
scanning of the kidneys, the adrenal gland and the brain.

An important use of iodine-123 is labelling meta-iodobenzylguanidine (MIBG).

This is used for diagnosing specific adrenal and brain tumours and associated
metastases (secondary tumours).
Gallium-67 has been in use since the late 1960s. It is used to detect infection,
inflammation and cancer, and to monitor the response of patients to treatment
for these conditions. In more recent times, it has been found that using fluorine18 deoxyglucose results in better quality images of soft tissue cancers. However,
gallium-67 can be produced in much larger quantities and transported longer
distances than FDG, which means it can be offered to far more patients.
Fluorine-18 is manufactured for PET studies and is chemically incorporated into
a glucose molecule to form FDG. Glucose is the basic energy source of the body
and particularly the brain, which uses glucose for all its energy requirements.
A radioactive glucose-like molecule in the form of FDG is the radiopharmaceutical
used predominantly for the diagnosis and monitoring of many forms of cancer.

The National Medical Cyclotrons

role in developing PET in Australia
The National Medical Cyclotron was the first centre to produce fluorine-18 for PET
studies in Australia. It was instrumental in establishing PET technology in Australia.
PET imaging has developed rapidly during the last decade, and mini-cyclotrons have
now been developed to manufacture the short half-lived positron-emitting radioisotopes
used in PET studies. These mini-cyclotrons operate on the same principle as
the National Medical Cyclotron and are designed for producing positron-emitting
isotopes, especially fluorine-18. They are not powerful enough to produce other
isotopes used for SPECT imaging such as thallium-201. There are now cyclotrons
in Sydney, Brisbane, Melbourne and Perth. These are designed specifically for FDG
manufacture and provide an efficient service to many nuclear medicine centres.
The National Medical Cyclotron still produces FDG for many centres, but its role in
PET imaging is changing as mini-cyclotrons are introduced. It is anticipated that its
future role in PET studies will be in the development of new tracers. New tracers
are likely to be able to trace other metabolic pathways in a manner similar to the
way that FDG traces the glucose metabolism.
The National Medical Cyclotron underwent significant upgrades to its ion source
and production systems in 2004. This will enable the cyclotron to efficiently
produce medical isotopes for the next decade, meeting Australias needs for
radioisotopes which can only be produced with high energy beams.

Cyclotrons and reactors

Cyclotrons produce radioisotopes which complement those manufactured in
nuclear research reactors.
The nucleus of an atom contains two types of particles neutrons and protons.
Stable atoms have a balanced ratio of neutrons and protons in the nucleus,
whereas in unstable atoms this ratio is unbalanced. The nucleus in an unstable
atom moves to become stable by the emission of particles or radiation, and is
hence called radioactive. When scientists make radioactive atoms they do this
by adding either extra neutrons or extra protons.
Atoms with extra neutrons in the nucleus are called neutron-rich and are
produced in a nuclear reactor. Atoms with extra protons in the nucleus are called
neutron-deficient and are produced in a particle accelerator such as a cyclotron.
Neutron-rich and neutron-deficient radioisotopes decay by different means and
hence have different properties and different uses. It depends on the radioactive
properties required whether a nuclear reactor or a cyclotron is used to produce
the radioisotope.
Both types of radioisotopes are needed to service all of Australias medical needs.
The most commonly used radioisotope, molybdenum 99-m (which decays into
technetium 99-m) can only be produced in a research reactor, for instance. Also, the
emerging generation of therapeutic isotopes can only be produced in a reactor.

The National
Medical Cyclotron
was instrumental
in establishing PET
technology in Australia.

For more detailed information on cyclotrons go to

www2.slac.stanford.edu/vvc/accelerators/circular.html
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Australian science, please provide your details to ANSTO at
enquiries@ansto.gov.au or (02) 9717 3770.

ANSTO

PMB 1
Menai NSW 2234
www.ansto.gov.au
October 2004