Nuclear - Medicine Všeobecne Prez

Medical
Applications of
Nuclear Sciences
Ilham Al-Qaradawi
Professor of Physics, Qatar University
Director, Qatar Cyclotron Research Centre, Qatar Foundation

Outline
• History of Physics discoveries
• Physics tools applied to medicine
• Medical imaging
• SPECT
• Magnetic Resonance Imaging (MRI)
• CT
• PET and PET/CT
• Hadron therapy
• Summary
WNU-SI 2010 Oxford - UK

Use of ionizing radiation for medical
applications
• Medical applications of nuclear sciences are of

particular interest as they prove many theories
wrong.
• Proof that the damaging effect of radiation has itself
been of great use.
• Proof that basic science research is not a fantasy.
• It eliminates the boundaries between the various
sciences.

History of “Medical” Physics discoveries
The beginnings of modern physics marks the beginning

of nuclear physics and of also of medical physics
1895 discovery of X rays 1896 Discovery of
Wilhelm Conrad Röntgen natural Radioactivity

Henri Becquerel

J.J. Thompson 1897 1898 Discovery of Po and Ra

discovery of the electron Marie Curie & Pierre Curie

1932 1932 – C. D. Anderson

Discovery of the neutron Discovery of the positron
James Chadwick

Physics tools applied to medicine:
The cyclotron
• 1930: invention of the cyclotron

• Ernest Lawrence
• 1 MeV cyclotron

The Synchrotron
1945 The Synchrotron
1945: E. McMillan & V.J.Veksler
discover the principle of phase stability
1 GeV electron synchrotron

Frascati - INFN - 1959
6 GeV proton synchrotron

Bevatron - Berkeley - 1954

Electron Linac
• 1947
• linac for electrons
• 4.5 MeV, 3 GHz
• William W. Hansen

Nuclear Magnetic Resonance (NMR)
NMR 1954
Felix Bloch and Edward Purcell
Felix Bloch
First CERN Director General
Two main areas of use
• Medical Imaging: technique of creating

images of internal human body or its
functions
• Radiation (and particle)Therapy:
Medical applications
• Diagnostic; Medical imaging (Radiology)
• X-rays and CT
• Magnetic Resonance Imaging (MRI)
• PET and PET/CT, PEM
• Treatment; Conventional radiation therapy
• Hadron therapy
• Antiproton therapy
Types of Medical Imaging
• Anatomical Imaging
• Functional Imaging
• Molecular Imaging

Anatomical Imaging
• X-ray
• MRI
• CT

X-ray Radiography
• Radiography involves the use of an X-

ray tube and a photographic plate.
• The patient is placed between the two

and an image is produced on the film
of the area exposed.
• A common “chest X-ray” is an

example of a radiographic X-ray.

Fluoroscopic x-ray imaging
• In a fluoroscopic X-ray machine the film cassette is
substituted with an imaging device (image intensifier)
which enables the radiologist to observe the part of the body
exposed live on a video monitor.
• A blocking agent, such as barium, is often swallowed by the

patient to allow the medical staff to observe internal
processes in action.
• A fluoroscopic examination can be used to locate ulcers.

X-ray image versus CT scan
• A conventional X-ray
image gives a shadow of
the body
• organs and tissues of
different densities show
up differently on the
radiographic film.
• Depending on where the
lamp is, you see the
outline of the pineapple or
the banana.
X-ray computerized tomography (CT)
COUNTS
DETECTOR
X RAYS
TUBE
A – LINEAR SAMPLING B – ANGULAR SAMPLING C - RECONSTRUCTION
This is the basic idea of

computer aided
tomography. In a CAT scan
machine, the X-ray beam
moves all around the
patient, scanning from
hundreds of different
angles. The computer
takes all this information
and puts together a 3-D
image of the body. X RAYS
COMPUTERIZED TOMOGRAPHY
Nuclear Medicine
• Radionuclides are used to determine the
extent of a medical problem in a patient.
• The radionuclide is “attached” to a

pharmaceutical, which has the properties to
deposit the radioisotope in the organ of
concern for a patient.
• External radiation detectors are used to

determine abnormalities in the organ.
• Thyroid scan and lung function tests are

examples.

Tracer techniques
• Different parts of the human body absorb different
elements but do not discriminate between different
isotopes.
• In tracer techniques a radioactive isotope of an element,
such as iodine, is injected into the body.
• The signals coming from the ensuing radiation then give
a picture of the size and location of the area where the
isotope was absorbed.
• Usually isotopes of a relatively short half-life, of the
order of minutes or days, are used to minimize long-term
radiation damage.
Medical radionuclides
• Radionuclides are used in medicine
by two general classifications:
– Nuclear Medicine for diagnostic
procedures
– Radiation Oncology for radiation
therapy.
• Nuclides used for
radiopharmaceuticals:
– should decay by emitting only photons
– Should have a short effective half-life.
– Technetium-99m and Indium-113m are
commonly used radiopharmaceuticals.
Functional Imaging
• Reveal structure
through function
• Image produced
depends on biological
distribution of
compound in vivo

Gamma Camera
• Used to record emitted internal radiation from
injected isotope to create two dimensional images.

Molecular Imaging
• Involves an imaging modality (MRI, ultrasound,

PET, etc.) and specially designed probes that
bind to and reveal specific biological targets
• Enables scientists and clinicians to visualize
specific biological processes non-invasively in
vivo.

Magnetic Resonance Imaging (MRI)
MAGNETIC FIELD: 1.5 – 3

Tesla
1H
SPIN
H2O
B B B
0 0 0
M M
M
RF
PULS MRI
E SIGNA
L
Magnetic field applied EXCITATION RELAXATION

Magnetic Resonance Imaging (MRI)
• MR image is a map of protons in water (most of

human body), with intensity determined by local
physical environment.
• Contrast and image quality are determined by
– Pulse sequence
– Field strength
– Shim quality
– Acquisition time

Magnetic Resonance Imaging: morphology
MRI of upper MRI of knee

torso (courtesy
NASA)
MRI of
shoulder
SPECT (Single photon emission computed tomography)
• Uses gamma cameras, or multi-
heads slowly rotated around the
patient.
• Able to provide true 3D
information.
• Information presented as cross-
sectional slices.
• 85% of all nuclear medicine
examinations use Mo/Tc Generators
for diagnostics of liver, lungs,
bones.
SPECT & PET
• 1983William Eckelman
and Richard Reba
carried out the first
successful SPECT
imaging of a
neuroreceptorin humans. Richard Reba
• 1983 Henry Wagner

carried out the first
successful PET imaging
of a neuroreceptor
Henry Wagner
Cyclotrons vs. Reactors
Cyclotron Reactor
charged particles neutral particles
short lived isotopes longer lived isotopes
neutron deficient nuclei neutron rich nuclei

Medical Isotopes
• Other isotopes can be made with cyclotron

particle accelerators
Cyclotron Target Isotopes Tracer Clinical Detector

Mo-99 from reactors
• Mo-99 is the most “in demand” medical isotope
• Mo-99 is shipped around (66 hrs half life)
• its “decay product” Technetium-99m is used as
tracer
• Comes “easily” from a handful of existing,
publicly funded nuclear research reactors
• Reactors are getting old

Crisis of 99Mo
• 30 million examinations/year rely on 99Tc
• Worldwide production of 100 000 curies per
year produced at aging nuclear reactors
– BR2 Belgium
– National Research Universal (NRU) Reactor Canada
(50%)
– OSIRIS France
– HFR Netherlands (40%)
– SAFARI-1 South Africa
• Canadian NRU off for repairs since middle of
last year
• Netherlands down for repairs
• Almost 90% of world Mo supplied by 2 closed
reactors
Radiochemistry
• Medical isotopes
separated under sterile
conditions
• Radiation dose to
operator must be
minimized
• Must be completed
quickly (less than one
half-life)
Positron Emission Tomography (PET)
Cyclotron
Radiochemistry J. Long, “The Science Creative Quarterly”,scq.ubc.ca

PET scans
• PET (positron emission tomography)
scans involve the injection into the
body of an isotope which decays by
positron emission.
• When this positron encounters an
electron they annihilate each other,
emitting two photons.
• The energy and path of these photons
leaving the body can then be used to
give an accurate picture of the area
where the isotope was absorbed.

PET
• When a pair of detectors detects
simultaneously one 511keV photon
each, a positron must have annihilated
on a straight line connecting those two
detectors – the so called line of response.
• The multitude of all these lines of
response is used to calculate a slice
image in a certain plane.
• produces a three-dimensional image or
picture of functional processes in the
body
PET Applications
• Oncology:
– Thyroid
– Sarcoma
– Lung
– Melanoma
– Lymphoma
– Head & neck
– Breast
• Neurological Applications:
• Parkinson’s, Alzheimer’s, Addiction

PET functional receptor imaging
Normal Subject
Parkinson’s disease
[11C] FE-CIT
Courtesy HSR MILANO
PET Isotopes
Nuclide Half-life Tracer Application
O-15 2 mins Water Cerebral blood flow
C-11 20 mins Methionine Tumour protein synthesis
N-13 10 mins Ammonia Myocardial blood flow
F-18 110 mins FDG Glucose metabolism
Ga-68 68 min DOTANOC Neuroendocrine imaging
Rb-82 72 secs Rb-82 Myocardial perfusion

FDG
• Most widely used PET tracer
• Glucose utilization
• Taken up avidly by most tumours
• Must be completed quickly (less than one half-
life)

Radiopharmacy
• To generate images, a small amount of
a radiolabeled compound (about 1-10
ng) is administered to the patient prior
to scanning
• The small amount used allows
biochemical processes to be studied
without perturbing the system (The
Tracer Principle)
• Take a medical isotope and make it
into a clinically useful compound?
• Chemistry, Chemical Biology and
Chemical Engineering
Instant Kits
• Instant kits provide cold, lyophilized product that

can be mixed with the isotope on site immediately
prior to delivery to the patient.

Mammography PET (PEM)
• Clear Crystal Collaboration (CCC) at CERN is now
working on a dedicated PET for mammography (breast
imaging), the ClearPEM.
• The aim is to be able to depict small tumors with a diameter
of 1mm to 2mm in the breast and axilla region.
• Advantages of PEM over x-ray mammography and whole
body PETs employed in hospitals at the moment are
multifold.
• Since tumor specific pharmaceuticals are used, the
probability of false diagnosis due to the presence of
inflammation, which is indiscernible from cancer on a
conventional x-ray, is reduced considerably.
PET/CT
• Combines the functional information with the

anatomical detail
• Accurate anatomical registration
• Higher diagnostic accuracy than PET or CT
alone
• CT was invented in 1972 by Godfrey Hounsfield
of EMI Laboratories

Pioneers
Michel Ter-Pogossian prepares a radiopharmaceutical for an examination

of Henry Wagner Jr with one of the first PET- scanners (1975)

Mobile PET

Cyclotrons used in medicine
• Baby Cyclotrons (< 18 MeV) in-house facility
• Mainly used for production of short-lived positron emitters
like 18F, 11C, 13N, 15O.
• Medium Energy Cyclotrons (< 40 MeV), centralised facility
• Majority of the cyclotron produced isotopes are produced
using such machine viz, 123I, 201Tl, 67Ga, 68Ga, 103Pd etc.
• High Energy Cyclotrons (above 40 MeV), centralised
facilities and research institutions
• Used for production of few radioisotopes requiring high
energy for production viz, 67Cu, 82Sr, 211At…
Accelerators for all stages
• Isotope production
• In diagnostics
• and endotherapy

Types of Accelerators
• Cyclotrons
• Syncrotrons
• Linacs

Three classes of medical accelerators
Electron linacs for conventional radiation therapy, including advanced

modalities:
•Cyberknife
•IntraOperative RT (IORT)
•Intensity Modulated RT
Low-energy cyclotrons for production

of radionuclides for medical diagnostics
Medium-energy cyclotrons and

synchrotrons for hadron therapy with
protons (250 MeV) or light ion
beams (400 MeV/u 12C-ions)
Baby Cyclotrons
• Accelerated protons

Medium energy cyclotrons

High-energy cyclotrons
• IBA‟s ARRONAX in
Nantes
• 4 Particles: H- / D- / He2+/
HH+
• Variable energy: 15 MeV
70 MeV

Medical accelerators: electron linac
Varian Clinac 1800 installed

in the S. Anna Hospital in
Como (Italy)

CyberKnife (CK) Robotic Surgery System
6 MV Linac mounted on a robotic arm
• The CyberKnife system is a

method of delivering
radiotherapy, with the
intention of targeting
treatment more accurately
than standard radiotherapy.
http://www.accuray.com/Products/Cyberknife/index.aspx
Radiation therapy
• Radiation is used to destroy tumors present in a

body. Damage to healthy cells is controlled by
using radioactive samples with specific half-lives
which subsequently are intended to decay in the
vicinity of the tumor when injected into the body.

Radiation oncology
• Radiation Oncology (study/treatment of tumors) uses
radionuclides for tumor treatment.
• Cobalt-60 is generally used for the high activity sealed

source.
• This consists of a mechanical device, which moves the

source to an opening in a collimator which projects a beam
of photons used for treatment.

Intensity Modulated Radiation Therapy
(IMRT)
• IMRT: advanced mode of high-precision radiotherapy utilizing
computer-controlled linac to deliver precise radiation doses to a
malignant tumor or specific areas within the tumor.
• Allows for the radiation dose to conform to the 3D shape of tumor.
• Allows higher radiation doses to be focused to tumor regions while
minimizing the dose to surrounding normal critical structures.
• Treatment planned by 3-D CT images of the patient in conjunction
with computerized dose calculations to conform to the tumor shape.
• The ratio of normal tissue dose to tumor dose is reduced to a
minimum, hence, higher and more effective radiation doses can safely
be delivered to tumors with fewer side effects

Intensity Modulated Radiation Therapy
An example of intensity
modulated treatment
planning with photons.
Through the addition of
9 fields it is possible to
construct a highly
conformal dose
distribution with good
dose sparing in the
region of the brain stem
(courtesy of T. Lomax,
PSI).
WNU-SI 2010 Oxford - UK E. Pedroni, Europhysics News (2000) Vol. 31 No. 6

Hadron therapy: n, p and C-ion beams
Charged hadrons have a much better energy deposition with respect to X-rays
“hadrons” are
made of quarks

Cancer therapy with photons, electrons
and hadron beams
• Linear accelerators
• In the world radiation
oncologists use 15000
electron linacs
• 40% of all the existing
accelerators.
• Beams of protons to
deliver more targeted,
precise doses
Protons and ions spare healthy
tissues
• Unlike photons or electrons,
proton beams deposit most of
their energy at the end of their
paths in the so-called Bragg
peak. Hence, targeting deep-
seated tumours, close to sensitive
organs, with much reduced risk
to surrounding healthy tissue.
• benefit of proton and heavy-ion
therapy is that the beams can be
"tuned" to deliver a high dose of
energy at a precise location

Proton therapy: cyclotrons and
synchrotrons
• Proton therapy is booming

Therapy with carbon ions
• Carbon allows extremely precise targeting of the
tumour.
• lighter particles such as protons, whilst
depositing their energy in the Bragg peak, cause
far fewer double-strand breaks than heavier
ones like carbon.
• Tumours eligible for carbon ion radiotherapy so
far are: skull base tumours and tumours close to
the spinal chord.
HIMAC in Chiba, Japan is the pioneer of
carbon therapy
• Japan has pioneered the use of carbon ions in the treatment of
tumours, treating the first patient in 1994.
• A new facility has come on line and others are under construction.
• HIMAC was the world's first heavy-ion accelerator facility
dedicated to medical use.
(Prof. H. Tsujii)

Germany: the GSI pilot project
• 1998-2009
• The GSI facility will be used for a
pilot project to treat several
hundred patients over a five-year
period.
• A typical course of treatment
involves around 20 half-hour
sessions on 20 consecutive days.
• The GSI facility is the first to
provide extremely precise tumor
conformity using magnetic beam
scanning in two dimensions
WNU-SI 2010 Oxford - UK http://cerncourier.com/cws/article/cern/27920

Future Facilities
• GSI Pioneer work (with HIMAC) in carbon-therapy
• CNAO, Pavia, Carbon Facility.
• Building Accelerator based on the PIMMS design
(CERN)
• ETOILE Carbon-Therapy facility, Lyon, France
• Heidelberg Ion Therapy, Germany.

The Hyogo “dual” Centre
• End of 2008
• protons: 2000 patients
• carbon ions: 500 patients

Heidelberg Ion Therapy

PIMMS (Proton Ion Medical Machine
Study) at CERN from 1996 to 2000
• Ugo Amaldi drew the interest of the
CERN management to the design of
an ion synchrotron optimized for
such a medical application
• CNAO, Pavia, Carbon Facility is
building accelerator based on the
PIMMS design (CERN).

Therapy is Commercialized
• Electron, proton and heavy ion accelerators for

radiotherapy and hadron therapy are now built (and
operated) by industry.
• Several companies have demonstrated that they can
built very performing accelerator turnkey facilities
with medical assurance quality standards for the
best price.

Antiproton Cancer Therapy
• Researchers at CERN have found that the antiproton, can effectively
treat cancer.
• Antiprotons strip electrons off atoms in the cells, causing ionization
and killing the cell they are in.
• A proton beam could also be used for ionization but when antiproton
beam eventually come to a stop at the focus, the annihilation of both
particles will release a huge amount of energy (in the context of a
single cell)....which is much more effective at killing selected cells
than simple ionization.
• Scientists estimate that routine clinical application of matter-
antimatter annihilation to cancer treatment should be a reality in 10-15
years.
Conclusions
• Medical applications are Multi-disciplinary; can only be
developed by collaboration between academic and medical
Research, industrial Development and Commercialization.
• New isotope production and separation techniques are
needed to provide a steady supply of medical isotopes.
• Accelerators may solve the technetium crisis.
• Automation, robotics, and technology are necessary aspect.
• Molecular imaging is enhancing health care by providing
early detection and better treatment of tumors with less side
effects on healthy tissue.
Takeaway points
• The progress in the field of radiation applications is not only driven by
advancement of nuclear and radiation physics but also by the
development of technology, to what extent is this valid?
• Better planning, research and cooperation worldwide are required to
avoid future radioisotope production crisis such as Mo-99.
• What seemed to be pure or basic science research in the past have had a
lot of impact on applications of medical imaging.
• Research is required to find techniques to reduce the damaging effects on
healthy cells and target diseased cells more effectively.
• Do scientists really need to use antimatter for cancer treatment? Bearing
in mind that it is the most expensive substance on earth; in 1999 the
estimated cost for 1g of antimatter was about $62.5b, and is very rare;
only 9 nanograms of antimatter are produced so far in all labs.
Questions?
Thank you for your attention
ilham@qu.edu.qa

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Medical

Director, Qatar Cyclotron Research Centre, Qatar Foundation

WNU-SI 2010 Oxford - UK

• Medical applications of nuclear sciences are of

WNU-SI 2010 Oxford - UK

The beginnings of modern physics marks the beginning

Wilhelm Conrad Röntgen natural Radioactivity

WNU-SI 2010 Oxford - UK

J.J. Thompson 1897 1898 Discovery of Po and Ra

WNU-SI 2010 Oxford - UK

1932 1932 – C. D. Anderson

WNU-SI 2010 Oxford - UK

• 1930: invention of the cyclotron

WNU-SI 2010 Oxford - UK

1 GeV electron synchrotron

6 GeV proton synchrotron

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

• Medical Imaging: technique of creating

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

• Radiography involves the use of an X-

• The patient is placed between the two

• A common “chest X-ray” is an

WNU-SI 2010 Oxford - UK

• A blocking agent, such as barium, is often swallowed by the

• A fluoroscopic examination can be used to locate ulcers.

WNU-SI 2010 Oxford - UK

A – LINEAR SAMPLING B – ANGULAR SAMPLING C - RECONSTRUCTION

This is the basic idea of

• The radionuclide is “attached” to a

• External radiation detectors are used to

• Thyroid scan and lung function tests are

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

• Involves an imaging modality (MRI, ultrasound,

WNU-SI 2010 Oxford - UK

MAGNETIC FIELD: 1.5 – 3

Magnetic field applied EXCITATION RELAXATION

• MR image is a map of protons in water (most of

WNU-SI 2010 Oxford - UK

MRI of upper MRI of knee

• 1983 Henry Wagner

WNU-SI 2010 Oxford - UK

• Other isotopes can be made with cyclotron

Cyclotron Target Isotopes Tracer Clinical Detector

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

Radiochemistry J. Long, “The Science Creative Quarterly”,scq.ubc.ca

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

O-15 2 mins Water Cerebral blood flow

C-11 20 mins Methionine Tumour protein synthesis

N-13 10 mins Ammonia Myocardial blood flow

F-18 110 mins FDG Glucose metabolism

Ga-68 68 min DOTANOC Neuroendocrine imaging

Rb-82 72 secs Rb-82 Myocardial perfusion

WNU-SI 2010 Oxford - UK

WNU-SI 2010 Oxford - UK

• Instant kits provide cold, lyophilized product that

WNU-SI 2010 Oxford - UK

• Combines the functional information with the