Download Selective Internal Radiation Therapy

MEDICAL PHYSICS
SCIENCE TEACHERS
WORKSHOP 2010
Kathy Willowson
[email protected]
Institute of Medical Physics, Sydney University
Department of Nuclear Medicine, Royal North Shore Hospital
Key areas in medical physics
Ultrasound, Radiology, MRI,
Nuclear Medicine
Diagnostic Imaging
Particle transport and
interaction with matter
Instrumentation – detection,
image formation
Image analysis – qualitative, quantitative
Key areas in medical physics
Ultrasound, Radiology, MRI,
Nuclear Medicine
Diagnostic Imaging
Particle transport and
interaction with matter
Instrumentation – detection,
image formation
Image analysis – qualitative, quantitative
Mechanisms of dose absorption
Treatment planning – xRT,
SIRT, radioimmunotherapy…
Radiation safety
Therapy and Dosimetry
Today’s workshop
• Comparison of diagnostic imaging techniques
• Functional vs Anatomical imaging
• Radionuclides for therapy
• Dosimetry: Calculating dose to organs during
diagnostic and therapeutic studies
• Dosimetry and radiation safety: putting dose in
perspective
• Quantitative PET in the treatment of cancer
Function vs Structure
Portable, cheap
Real time
No radiation
No contrast agent
Multi-planar imaging
Evaluate blood flow
Cysts vs solid structures
Function vs Structure
Portable, cheap
Poor quality
Real time
Experience needed
No radiation
Only shows anatomy
No contrast agent
Difficult for obese
Multi-planar imaging
Deep lying structures
Evaluate blood flow
Can’t see through
Cysts vs solid structures bone/air
Function vs Structure
Portable, cheap
Poor quality
Real time
Experience needed
No radiation
Only shows anatomy
No contrast agent
Difficult for obese
Multi-planar imaging
Deep lying structures
Evaluate blood flow
Can’t see through
Cysts vs solid structures bone/air
No toxic contrast
No radiation
V good resolution
Exquisite detail in soft
tissue
fMRI
Function vs Structure
Portable, cheap
Poor quality
Real time
Experience needed
No radiation
Only shows anatomy
No contrast agent
Difficult for obese
Multi-planar imaging
Deep lying structures
Evaluate blood flow
Can’t see through
Cysts vs solid structures bone/air
No toxic contrast
No radiation
V good resolution
Exquisite detail in soft
tissue
fMRI
Expensive
Claustrophobia
Mag field safety
Lengthy exams
Less detail in bone
Function vs Structure
Anatomical detail
All structures
Readily available
Fast
Function vs Structure
Anatomical detail
All structures
Readily available
Fast
Radiation dose
May use contrast
Artifacts from metal,
obese patients
Anatomical only
Function vs Structure
Anatomical detail
All structures
Readily available
Fast
Radiation dose
May use contrast
Artifacts from metal,
obese patients
Anatomical only
Functional images
See early changes
Can delineate between
active tumour and
scarring
WB scanning
Quantitative
Function vs Structure
Anatomical detail
All structures
Readily available
Fast
Radiation dose
May use contrast
Artifacts from metal,
obese patients
Anatomical only
Functional images
See early changes
Can delineate between
active tumour and
scarring
WB scanning
Quantitative
Radiation dose
Little anatomy
Limited resolution
Need specific
tracers
Function vs Structure
Function vs Structure
Function vs Structure
Function vs Structure
WB functional imaging
shows abnormal
uptake in 3 areas.
The large focus is
clearly off-centre and
probably a soft tissue
mass
Function vs Structure
Function vs Structure
Function vs Structure
Physics of Nuclear Medicine
• The tracer principle: Radioactive isotopes have the
same chemical properties as non-radioactive isotopes of
the same element. They differ only in the number of
neutrons in their atoms which leads to different stabilities.
Unstable nuclei gain stability by radioactive decay, which
results in the emission of different types of particles.
When introduced to the body, a radioactive isotope will
behave in the same way that its non-radioactive
counterpart would.
• As a radioactive isotope participates in a certain
physiological process in the body, it will emit radiation
particles – allows us to image the process as it occurs.
Physics of Nuclear Medicine
• Tissue specificity: Specific tissues in the body will
accumulate specific substances. Labelling one of these
substances with a radioactive isotope leads to
information on certain tissues or organs of interest.
• EXAMPLE - the Thyroid gland: The thyroid removes
Iodine from the blood and traps it, where it is processed
and used to create thyroid hormones. When we inject I123 into the blood, it behaves as any isotope of Iodine,
and is taken up by thyroid tissue. However, it also emits
gamma radiation which can be detected and used to
analyse whether or not the thyroid is functioning
correctly.
Physics of Nuclear Medicine
• Radioactive isotopes can emit different types of
radiation: gamma rays, x-rays, positrons, electrons
(beta), alphas…
• Radioactivity used for imaging must escape the body
Physics of Nuclear Medicine
Single Photon Emission
Computed Tomography
(SPECT) detects gamma
rays emitted by a
radioisotope in the body
Positron Emission
Tomography (PET)
detects gamma rays
created by a positron
emitting radioisotope
head
Physics of Nuclear Medicine
• Radioactive isotopes can emit different types of
radiation: gamma rays, x-rays, positrons, electrons
(beta), alphas…
• Radioactivity used for imaging must escape the body
• Radioactivity used for therapy must be contained in the
body
• Alpha and Beta particles are ideal for therapy because
they are heavy and slow – do a lot of damage in a
localised area
Radionuclide Therapy
Alpha particles can irradiate tissues with cellular dimensions,
are very effective due to their high LET and can kill cells even
in a hypoxic environment
Beta particles can irradiate multi-cellular dimensions
Advantages of Radionuclide Therapy
• Systemic treatment: Eliminates primary tumour and
other sites of metastasis that have spread through the
body – even if they are yet to be detected with diagnostic
imaging
• Beta’s have the additional feature of the “bystander
effect” – they will kill adjacent tumour cells, even if these
cells lack the specific tumour-associated antigen or
receptor
Treatment of Thyroid Cancer
• I-131 is a beta and gamma emitter
• Patient takes a capsule of liquid I-131 which is
absorbed through the gut into the bloodstream, before
concentrating in thyroid tissue
• Due to its specificity, very large doses can be given
• Beta particles mean very localised damage
• Gamma particles mean it can also be used to image
distribution of uptake
• Systemic treatment – targets ALL thyroid tissue cells –
even those that have metastasized elsewhere
Treatment of Thyroid Cancer
Normal uptake in gut,
bladder and salivary glands
Uptake in remaining
cancerous thyroid tissue
Uptake at sites of
metastases
Treatment of Thyroid Cancer
• The body will naturally distribute/take-up 131I
• It will also naturally excrete 131I (body fluids – urine)
• The PHYSICAL half life of 131I ~ 8 days
• The BIOLOGICAL half life is much faster (10-15 hours)
• After a therapeutic dose of 131I, about 75% is excreted in 24hrs
• The 131I trapped by thyroid tissue is much slower to leave
• This uptake/excretion is used to model how much activity
should be given to a particular patient
• Slow excretion of the remainder = radiation safety issues
Treatment of Thyroid Cancer
-
Beta emitter:
Contamination through body fluids can easily occur
Patient must not vomit in first 24hrs
Flush toilet twice and obey good hygeine practice (wash
hands well, use separate bathroom if possible)
Do not prepare food for others

Gamma emitter:
-
Distance / Time for visitors is important
-
Discharge limit = 9mSv/hr at 2m or 25mSv/hr at 1m
-
Transport after discharge must be arranged with a family
member / carer (NOT public transport)

-
Treatment of Thyroid Cancer
FOR 1 WEEK AFTER DISCHARGE:
-
Avoid being around members of the public for extended
periods of time (transport, cinema, shopping centres)
-
Sleep alone
-
Keep extra distance with family members
FOR 2 WEEKS AFTER DISCHARGE:
-
Keep additional distance and only spend short periods of
time with children and pregnant women
-
Delay return to work for this additional week if working
with children
Selective Internal Radiation Therapy
• SIRT involves selective uptake of a radionuclide at the site of
disease, usually by “force”
• SIR-Spheres: resin microspheres labeled with 90Y
• 90Y is a pure beta emitter – ideal for therapy if we can get the
microspheres at the site of disease (liver)
• Millions of the radioactive microspheres (~30mm in diameter)
are injected through a catheter inserted into the hepatic artery
• Become concentrated in the microvasculature of the tumour
and deliver a very high/localised dose
Selective Internal Radiation Therapy
Selective Internal Radiation Therapy
• Important questions for therapy:
- How much activity do we administer?
- What dose does the tumour receive?
- What dose is given to healthy tissue?
- Is this acceptable/can it be improved?
- What is the risk associated with this dose?
Selective Internal Radiation Therapy
How is dose related to activity?
Absorbed
Dose in the =
target organ
Total amount of energy emitted by the
source organ x the fraction of that energy
absorbed in the target organ
Mass of the target organ
Selective Internal Radiation Therapy
~
D  AS
Where à = cumulated activity (the sum of all transitions
occurring in the source organ over the residence
time)
S = the fraction of energy emitted by the source
that is absorbed per unit mass of the target
Selective Internal Radiation Therapy



This equation is deceptively simple
Must also consider dose from multiple source organs
(summation)
Cumulated activity relies on the “effective half life” (Teff)
of the activity which must be modeled based on physical
half life and biological clearance:


0
0
~
eff t
A   A(t )dt   fA0e dt  1.443 fA0Teff
1
1
1


Teff Tphys Tbiol
Selective Internal Radiation Therapy
Longer “half life” (both
physical and biological)
= Larger area under
time activity curve
= Larger cumulated
activity
= Larger dose
Selective Internal Radiation Therapy
S = fraction of energy emitted by the source that s absorbed by
the target
Units = Gy.MBq-1.sec-1 where Gy (Gray) = absorbed dose
S values range from simple approximations (whole organ
irradiated uniformly) to complex calculations (voxel dose
kernels for convolution)
Published S value for 90Y in the liver (average mass = 1910g)
for an adult male = 7.83x10-5 mGy/MBq-sec
Selective Internal Radiation Therapy
PROBLEM: What is the absorbed dose to the liver from a SIRT
involving 1800MBq of 90Y? Assume all the implanted activity
remains in the liver and is uniformly distributed.
ANSWER:
D = Ã.S
à = 1.443. f.A(0).T(eff)
= 1.443.(1800).T(1/2)
90Y
has a half life of 64 hours (230400 sec)
à = 5.98x10-8 MBq.sec
D = 46.9 Gy
The concept of dose

Absorbed dose (D): The energy deposited by ionizing
radiation per unit mass (all types of radiation), measured
in Grays (Gy). 1Gy=1J/kg
The concept of dose

Absorbed dose (D): The energy deposited by ionizing
radiation per unit mass (all types of radiation), measured
in Grays (Gy). 1Gy=1J/kg

Equivalent dose (H): The absorbed dose scaled by a
radiation weighting factor (wR) to take into account the
type of radiation and how much damage it causes,
measured in Sieverts (Sv). X-rays/g-rays/e- have a
weighting factor of 1 (1Gy=1Sv), a-particles have a
weighting factor of 20. Therefore 1mGy of alpha rad has
the same biological effectiveness of 20mGy of x-rays.
H  wR D
The concept of dose

Effective dose (E): Takes into account the weighting
factor of a given tissue (wT) as opposed to whole body
irradiation, measured in units of Sieverts (Sv) (=equiv
dose to tissue * tissue weighting factor). The gonads
have the highest weighting factor (0.2) as they are the
most sensitive to radiation, whilst skin is least sensitive
(0.01) (total sum of weighting factors across all tissues
= 1). Allows for comparison of radiation of different
types to different regions
E   wT  wR DT , R
The concept of dose
Tissue/Organ
wT
Tissue/Organ
wT
Gonads
0.20
Breast
0.05
Bone Marrow
0.12
Liver
0.05
Colon
0.12
Oesophagus
0.05
Lung
0.12
Thyroid
0.05
Stomach
0.12
Skin
0.01
Bladder
0.05
Bone Surfaces
0.01
Remainder
0.05
The concept of dose
PROBLEM: What is the effective dose to the liver from a SIRT
involving 1800MBq of 90Y? Assume all the implanted activity
remains in the liver and is uniformly distributed.
ANSWER:
D = Ã.S = 46.9 Gy
E   wT  wR DT , R
= 0.05(46.9 * 1)
= 2.4 Sv
The concept of dose
Is an effective dose of 2.4Sv / absorbed dose of 47Gy
acceptable?
• Tumour dose -> 100Gy, healthy tissue doses ->???
• Dose measures should be interpreted very carefully
• They are useful in the development of new
treatments/drugs and to compare existing treatments
• Play an important role in assessing risk vs benefit
The concept of dose
• Background radiation living in Sydney ~ 2mSv/year
• Dose limit for radiation workers = 20mSv/year (50mSv in US)
• Dose limit to public = 1mSv/year
• Chest x-ray <0.05mSv / Mammogram ~ 0.5mSv
• Return flight Sydney/London ~ 0.1mSv
• Nuc med studies ~ 1-10 mSv / x-ray CT studies ~ 1-20mSv
• Evidence for small increases in human cancer above
100mSv (acute exposure, or 200mSv chronic)
• Release of 131I cancer patients = 10mSv/hour at 1m
The concept of dose
• Be careful how you interpret dose!!!
• Age at exposure plays an important role
• Dose calculations have adopted the Linear No Threshold
model, which assumes a linear relationship between exposure
and risk
• There is no evidence to support this model for doses < 0.2Sv
• Some predict that the biological effect below a threshold
dose may in fact be reduced
• Acute vs chronic exposure also plays a part
PET SUV – response to therapy
• Medical physics plays an important role in nuclear medicine
for the evaluation and staging of disease, and monitoring
response to therapy
• The quantitative nature of PET allows for direct comparison
of uptake across different patients, or in the same patient at
different time points
• Standardised Uptake Value:
SUV =
Concentration (MBq/kg)
Injected activity (MBq) / Body weight (kg)
PET SUV – response to therapy
• SUV readings can be affected by: Recent chemotherapy,
uncontrolled glucose levels (diabetics), leanness of the body,
length of fasting prior to test, inflammation/infection,
resolution…
• Commonly used to indicate benign from malignant lesions:
Normal tissue has an SUV=1.0. Lesions with an SUV > 2.5 are
likely to be malignant, however lower SUVs can still be
malignant
• Used in staging and to look at response to therapy, and in
comparison of treatment regimes across a patient cohort
PET SUV – response to therapy
PROBLEM: A 70kg patient is injected with 280MBq of FDG at
time 8:15am. The patient undergoes a 10 minute PET scan at
9:30am. The doctor finds adrenal uptake with a concentration
of activity equal to 12.6kBq/ml. Is this likely to be a malignant
tumour?
ANSWER:
1) Measured concentration must be decay corrected back to
the same time which the injected dose was measured to
allow accurate comparison – FDG half life is 110mins
2) Calculate the SUV
PET SUV – response to therapy
ANSWER:
1) Measured concentration = 12.6 kBq/ml
Decay correct time = 80mins (to mid-scan time)
A = A(0) x e-t
For t1/2 = 110mins ---------------  = ln(2)/t1/2 = 0.0063
Decay corrected concentration = 20.9 kBq/ml
= 20.9 kBq/g
= 20.9 MBq/kg
2) SUV = (20.9MBq/kg) / (280MBq / 70kg) = 5.2
3) Abnormally high uptake – likely to be malignant
Conclusions
• Medical physics covers a very large area
• Physics plays an important role not just in diagnostics but
also in therapy – from understanding particle interactions to
concepts of dose and qualitative vs quantitative image
evaluation
• Being a medical physicist in the clinic covers a broad
range of duties – including image analysis, maintenance of
equipment, QC procedures, development of new
diagnostics/therapies, improving existing treatments,
radiation safety …
• Medical physics is an area that inspires great interest from
students and is applicable to those with skills from many
different backgrounds