Transcript What is Nuclear Medicine?

Nuclear Medicine:
Radionuclides,
Radiopharmaceuticals and
Radiation Protection
Katrina Cockburn,
Nuclear Medicine Physicist
What is Nuclear Medicine
 “Diagnostic imaging”
 “Radiotherapy”
 “Diagnostic testing”
 “Make people glow in the dark”
 Or… “Nurse”
What makes us different from:
 X-Ray?
 Linac Radiotherapy?
Function
What is Nuclear Medicine?
 a medical imaging technique in
which a pharmaceutical, labelled
with a radioactive substance, is
administered to the patient. The
amount of radioactivity in various
parts of the body is then
measured with a gamma camera
Why is this useful?
 Any imaging modality can show what is
there
 We use the body’s own physiology to
indicate and/or treat abnormalities which
would not be possible using conventional
radiology or radiotherapy
NORMAL BRAIN CT
BRAIN CT
THIS IMAGE
WAS ACQUIRED
POST-MORTEM
Why is this useful?
Why is this useful?
•CT stage
T3 No Mo
•PET/CT stage
T3 N2 Mo
Lymph Node <10mm
Images courtesy of Institute of Nuclear Medicine, University College London
Why is this useful?
•CT staging
T4 N2 Mo
•PET/CT staging
T4 No Mo
Images courtesy of Institute of Nuclear Medicine, University College London
Why is this useful?
 Additional value of PET-CT in the staging of lung cancer:
De Wever et al, 2007.
Tumour
Node
Met
TNM
PET CT
86%
80%
98%
70%
CT
68%
66%
88%
46%
PET
46%
70%
96%
30%
Co-Read
72%
68%
96%
54%
Over-staging:
PET-CT T=8%, N=16%, CT T=16%, N=20%
Under-Staging: PET-CT T=6%, N=4%, CT T=12%, N=6%
Components of NM Procedures
Radiopharmaceutical
Detection Device
Analysis
Radiopharmaceutical
 Two functions:
 Pharmaceutical – acts as tracer
 Radioactive material – allows us to monitor
distribution
 Both functions may be performed by the
radioactive isotope
 I-123 thyroid imaging
 Or isotope may need to be chemically bound to
a pharmaceutical
 Tc99m – HDP for bone scans
Properties of Radioactive Materials
 May emit x-rays, gamma-rays, electrons or
alpha particles
 There may be one or more of these emitted
 Daughter products may also be radioactive
 Gamma rays will have “characteristic”
energies
 Decay exponentially
The Ideal Radiopharmaceutical
 Pharmaceutical
 Short biological half-life
 Localise only in the
area of interest
 Should not alter
physiological system
under examination
 Minimal/No side effects
 Radionuclide
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Short physical half-life
Pure Gamma Emitter
Energy 100-200keV
Suitable for
incorporation into a
pharmaceutical
 Readily available
 Easy to prepare
 Labelling Stability
Mechanisms of Localisation In-Vivo
 Active Cellular Transport
 potassium analogues in myocardial imaging
 Simple diffusion
 Kr-81m in lung ventilation
 Capillary Blockade
 Tc99m-MAA for lung perfusion
 Physiochemical adsorption
 Phosphates localising in mineral phase of bone
 Antibodies
 Labelled antibodies for tumour imaging
Commonly Used Radionuclides
Radionuclide
Production
Half-Life
Generator
Photon Energy
(keV)
140
Tc99m
Tl201
Cyclotron
68-80 (x-rays)
74h
I123
Cyclotron
160
13h
In111
Cyclotron
173, 247
67h
F18
Cyclotron
511*
110 min
Rb82
Generator
511*
75 sec
I131
Reactor
280, 360, 640
8 days
* Annihilation photons produced in pairs
6h
Radionuclide Generators
 Solution to the problem of supply of shortlived radionuclides (e.g. Tc99m, Rb82)
 Principle:
Relatively long lived
parent radionuclide
Decay
Daughter radionuclide
with shorter half-life
Elution
 Remove ‘daughter’ radionuclide
 No removal of ‘parent’ radionuclide
 Sterile
 Techniques




Precipitation
Distillation
Ion exchange
+ Others
Mo99 Decay Scheme
Mo99 (T½ = 67h)
-
β (91.4%)
Tc99m (T½ = 6h)
-
β (8.6%)
γ
Tc99 (T½ = 2.1x105 years)
β
-
Ru99 (stable)
Ion Exchange
One-way air
filter
Mo99 Absorbed
onto Alumina
Evacuated
Vial
Filter
Eluent
Reservoir
Na+Cl-
Generator
Lead/ Depleted
Uranium Shield
Na+(TcO4)-
Tc99m Generator
120
Mo99
100
Activity
80
60
40
Tc99m
Transient
Equilibrium
20
0
0
24
48
72
96
120 144 168 192
Time (Hours)
Tc99m Generator with Elution
120
Mo99
100
Activity
80
60
40
Tc99m
20
0
0
24
48
72
96
120
Time (Hours)
144
168
192
Radio-Labelling with Tc99m
 Cold Kits
 Pre-packed set of sterile ingredients designed
for the preparation of a specific
radiopharmaceutical
 Typical Ingredients
 Compound to be complexed to the Tc99m
 e.g. methylene diphosphonate (MDP)
 Stannous Ions (Sn+)
 Stablilsers, buffers, antioxidants, bactericides
Cyclotron and PET isotopes
 Most PET isotopes are produced in
cyclotrons
 F18, C11, O15
 Positron emitters have “too many” protons
for stability
 Normally produced by smashing protons
into stable targets
 To make F18, fire protons into O18
enriched water
Nuclear Reaction for F-18
proton
Oxygen -18
Fluorine – 18
8 protons, 10 neutrons
9 protons, 9 neutrons
 Proton fired at oxygen-18
 O-18 absorbs the proton
 Temporary creation of fluorine-19
 Emission of neutron
 Creation of fluorine-18
neutron
Physics of the cyclotron
 Charged particles move in circles in a
static magnetic field
 The size of the circle depends on the
energy of the particle
 Electric fields can be used to accelerate
particles
 Cyclotron uses both types of fields to
accelerate a beam of protons into a target
Diagram of a cyclotron
ABT Desk-top cyclotron
Radiopharmacy QA
 Radionuclide Purity
}
 Mo99 ‘Breakthrough’
first eluate from each generator
 Aluminium
 Other Radioactive contaminants Quality guaranteed by
manufacturer
 (fission impurities)
 Radiochemical Purity
 Free Tc99m
 Different bio-distribution
 Unnecessary radiation of organs
 Misdiagnosis
}


First vial of new batch for
commercial kits
All kits for unlicensed products
 Sterility
 Aseptic techniques
 Routine monitoring for microbiological, particulate, and
radioactive contamination
Radionuclide Calibrator
 Ionisation Chamber
 Acceptance Testing
 Check against national or
secondary standards
 Daily QA
 Long Lived Source
 Source assayed using several radionuclide
settings
 Geometrical Dependence
Factors Affecting the Dose
 Administered Activity
 Diagnostic Reference Levels (ARSAC)
 Effective Half-Life
1

1

1
 effective  phys  biol
 Bio-Distribution
 Radiochemical purity
 Pathology
 Drugs
 Type of radioactive decay
 Energy of emissions
Patient Dosimetry
 The Cumulated
Activity: Ãs
 The activity of the
radiopharmaceutical
within a given organ
integrated over time
 Depends on the
effective half life
Patient Dosimetry
 The “S-Factor”, S
 Published by MIRD
 S(t,s) = D f(t,s) / m
 D = Total energy from the radiation type
 f(t,s) = the fraction of the energy absorbed by
the target organ (t) which is emitted by the
source organ (s)
 m = the mass of the target organ
Patient Dosimetry
 Dose to the target organ, Dt
 Takes into account dose from activity
within the target organ and all other
organs
Patient Dosimetry
 Need to account
for differing
radiosensitivities:
 Use ICRP
weighting factors
for different
organs to get the
Effective Dose, H
Radiopharmaceuticals and doses
Radiopharmaceutical
Route
Typical Activity
Effective
(MBq)
Dose (mSV)
Clinical Use
Tc99m-MDP
i.v.
600
3
Bone Imaging
Tc-99m-DTPA
Inhaled
20
0.1
Lung
Ventilation
Tc-99m-MAA
i.v.
100
1
Lung
Perfusion
Tl-201 (thallous
chloride)
i.v.
80
18
Myocardial
Perfusion
I-131-sodium
iodide
oral
400
24
Thyroid
metastases
Tc99m- labelled
red cells
i.v.
800
8
Cardiac blood
pool
Tc99m-labelled
white cells
i.v.
200
3
Localisation of
infection
Protection of the Patient
IR(ME)R
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
Referral Criteria
Justification (ARSAC license holder)
Patient identification procedures
Labelling of syringes/vials
Checking of activity prior to administration
Protective clothing
Thyroid Blocking
Conception, Pregnancy, Breast Feeding
Protection of the Patient
MARS and ARSAC
 Certification of medical and dental





practitioners
Certificates last for 5 years
Specific to individual practitioner
Specific to individual site
Named radiopharmaceuticals and uses
Notes for Guidance
Pregnancy
 Policy to check for pregnancy in female patients
of child bearing age
 Notices in departments “Please inform
technicians if you may be pregnant”
 Does the risk to the foetus outweigh the risk to
the patient from failure to diagnose and treat
 Clinical benefit to the mother may be of indirect
benefit to the unborn child
Conception: Advice to Males
 No evidence that pre-conceptual irradiation of
males can cause any abnormality in their
offspring*
 No need to avoid conception for males undergoing
routine diagnostic studies
 Therapeutic administration of long-lived
radionuclides (e.g I-131, Sr-89)
 Possible appearance of larger quantities of such
radionuclides in sperm
 Avoid conception for 4 months
*Doll
R et al. Nature 1994;367:678-680
Conception: Advice to Females
 No need to avoid pregnancy after diagnostic procedures
using radiopharmaceuticals with a physical half-life
<7days*
 Diagnostic use of Longer Lived Radiopharmaceuticals:
 Se75 (adrenal imaging): 12 months
 I131-MIBG (tumour imaging): 2 months
 I131 (thyroid metastases): 4 months
 Therapy
 I131 (≤800 MBq for treatment of thyrotoxicosis): 4 months
 P32 (≤200 MBq for treatment of polycythemia): 3 months
 Sr89 (≤150 MBq for treatment of bone metastases): 24 months
*ARSAC
Notes for Guidance Dec 1998 p25
Breast Feeding
 Can the test be delayed?
 Mother to express breast milk prior to test
 Advise to stop breast feeding for time
depending upon radiopharmaceutical
 Any I131-iodide: STOP
 80 MBq Tc99m-MAA: 12 hours
 800 MBq Tc99m-DTPA: 0 hours
Radiation Protection
IRR
 Time, Distance, Shielding
 Handling techniques to reduce time
 Forceps
 Syringe Shields
 Contamination
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

Surfaces in rooms to be smooth and non-absorbent
Isolators
Protective Clothing
No eating or drinking in rooms where unsealed
sources handled
 Wash hand basins close to the exit of rooms
 Routine contamination monitoring
 Room surfaces and staff leaving controlled areas
Radiation protection from patients
IRR
 In general no restrictions or precautions
for diagnostics procedures
 Exceptions:
 >10MBq In111-WBC, >120MBq In111 Octreotide
 >200MBq Ga67 citrate, >30MBq I-131
 If the work of the patient is radiosensitive
 Assessment of exposure and contamination risk
 Therapy
Procedures on Wards
 Contamination
 Ward staff will be protected if they follow
standard hygiene procedures (e.g.
gloves/aprons)
 Handling & storage instruction should
bedding/clothing become contaminated
 Direct Irradiation
 No special precautions usually required
 Risk assessment if patient require intensive
nursing
Keeping & Disposal of Radioactive
Substances
 EPR Certificates for storage and disposal
of radioactive materials
 Properly designed stores
 Stock Records
 Reports to be sent to the Environment
Agency
 Solid waste for incineration
 Solid waste to landfill
 Aqueous waste to drains
Transport of Radioactive Materials
 Controlled under Carriage of Dangerous
Goods 2009
 Drivers need to be
trained
 Vehicles need to be
marked
 Emergency kits and
instructions