1. Artificial WHY?? Revision What’s a radionuclide?
Principle of nuclear medicine
Medical Radionuclides:
Naturally occurring???
Man made?? Artificial??
Artificial
WHY??
4th lecture RAD 311
15/03/2010

2. RADIONUCLIDE PRODUCTION
Dr. Mohammed Alnafea

3. RADIONUCLIDE PRODUCTION
1. From stable isotopes
a. Charged particle irradiation
b. Neutron irradiation
2. From radionuclides (unstable)
a. Spontaneous fission
b. Radionuclide generator
4th lecture RAD 311
15/03/2010

4. Charged Particle Irradiation
4th lecture RAD 311
15/03/2010

5. Charged particle accelerators
Cyclotron
linear accelerator
accelerate charged subatomic particles (p, d, ) to high energy ( MeV)
This is necessary to overcome Coulombic energy barrier to insertion into nucleus
4th lecture RAD 311
15/03/2010

6. 1. Cyclotron
4th lecture RAD 311
15/03/2010

7. CTI RDS-111 Cyclotron
4th lecture RAD 311
15/03/2010

8. CTI RDS-111 Cyclotron Self-shielded design - no need for vault
shielding for attenuation of both  and n radiation
only 2 shields to move for accelerator access
safety-interlocked
4th lecture RAD 311
15/03/2010

9. Cyclotron Targetry target material 1. internal targets
Deposition vs. thin-walled target tubes
mg material in target tube; 10-50mg in solid target
1. internal targets
may reach temperatures near 1000°C - water cooling required
2. external beam targets
beam currents reduced due to inefficiency of beam extraction
reduced product yields vs. reduced cooling requirements
thermal power in target is product of beam current and projectile energy e.g. 20 MeV protons and beam current of 20µA = 4kW of power at target
target backplate made of good conductor for heat dissipation copper, silver, aluminium - usually water cooled
4th lecture RAD 311
15/03/2010

10. CTI RDS-111 Cyclotron Targetry
4th lecture RAD 311
15/03/2010

11. GENERAL CHARACTERISTICS OF CYCLOTRON
addition of +ve charge to nucleus leads to:
tendency to decay by + or E.C.
Z changes  allows separation of target and product atoms
product has high specific activity )carrier free)
low beam intensity of cyclotron
smaller quantities of product made than in other modalities e.g. reactors
expensive
4th lecture RAD 311
15/03/2010

12. CYCLOTRON PRODUCED RADIONUCLIDES
PRODUCT
DECAY MODE
PRODUCTION REACTION
11C β+
10B(d,n)11C
13N
12C(d,n)13N
15O
14N(d,n)15O
18F
β+, EC
20Ne(d,α)18F
67Ga
EC, γ
68Zn(p,2n)67Ga
111In
109Ag(α,2n)111In
123I
122Te(d,n)123I
201Tl
201Hg(d,2n)201Tl
15/03/2010
4th lecture RAD 311

13. 2. Linear Accelerators
4th lecture RAD 311
15/03/2010

14. Linear Accelerators
ION SOURCE
RADIO FREQUENCY
OSCILLATORS
ION BEAM
DRIFT TUBES
TARGET
acceleration occurs along linear rather than circular path
rarely used for production
specific applications due to high beam currents obtainable
89Sr, 125I + other brachytherapy sources
4th lecture RAD 311
15/03/2010

15. Educational Video
4th lecture RAD 311
15/03/2010

16. 1.b
Neutron irradiation
4th lecture RAD 311
15/03/2010

17. Nuclear Reactor
4th lecture RAD 311
15/03/2010

18. Nuclear Reactors two production processes - neutron bombardment
fission
reactors serve as a source of neutrons produced as a result of nuclear fission
reactors serve as a source of fission fragments
4th lecture RAD 311
15/03/2010

19. RADIONUCLIDE PRODUCTION Neutron bombardment
resistance to insertion of neutron into nucleus less than for proton
neutron capture by stable nucleus - (n,) reaction
produces neutron rich radionuclides
4th lecture RAD 311
15/03/2010

20. NUCLEAR REACTOR Schematic Representation
4th lecture RAD 311
15/03/2010

21. RADIONUCLIDE PRODUCTION Thermal neutron induced fission
235U is most commonly used fissionable material
235U + n  unstable nucleus  fission fragments + n + E
average number of neutrons per fission = 2.4
self-irradiation of 235U - self sustaining chain reaction
moderators included to slow neutrons to thermal energies - deuterium oxide, graphite
4th lecture RAD 311
15/03/2010

22. RADIONUCLIDE PRODUCTION Thermal neutron induced fission
235U fission  > 370 nuclides
observed mass range :
distribution as indicated
4th lecture RAD 311
15/03/2010

23. RADIONUCLIDE PRODUCTION Thermal neutron induced fission
radionuclides extracted when fuel elements replaced
chemical separation techniques used
precipitation, solvent extraction, chromatography
products usually (carrier free), high specific activity
fission produced radionuclides usually neutron rich
decay by - emission
relatively cheap - not major function of reactor
4th lecture RAD 311
15/03/2010

24. RADIONUCLIDE PRODUCTION Reactor Targetry
irradiation positions
mobile : short irradiation times (minutes - 1 week)
fixed : long irradiation times (one or more reactor fuel cycles : weeks)
accessible only during reactor shutdown
both positions water cooled
reactor temperature  100°C, sample temperature > 1000°C ( heating)
target design
pure element often best choice – high melting point and density
prevention of target rupture primary safety consideration
use of mercury and cadmium prohibited
reactivity of mercury with aluminium (fuel cans)
high neutron absorption of cadmium (reactor operation)
4th lecture RAD 311
15/03/2010

25. RADIONUCLIDE PRODUCTION Neutron bombardment
Activity of a radionuclide produced by particle bombardment is given by
A = N (1 - e-t)
where: A = activity
 = particle flux (number/cm2/s)
N = number of target atoms
 = absorption cross section in barns (10-24 cm2/atom)
 = decay constant of product radionuclide
t = duration of irradiation (in seconds)
when t > 4 x T½ , (1 - e-t) approaches 1
saturation activity : A = N
no gain from irradiating beyond x T½
4th lecture RAD 311
15/03/2010

26. RADIONUCLIDE PRODUCTION Preparation of I-131 (carrier)
Starting material : 2.5g 93+% 235U
flux: 2 x 1014n/cm2/sec, 28d
target stored for 7d following irradiation
dissolved in 4.5M NaOH + heating
133Xe released - trapped (charcoal, liquid N2)
Al2O3.2H2O + NaI
+ H2SO4 + H2O2 - distilled
 7500 GBq 131I (+ 127I + 124I) i.e. carrier iodine
235U recovered for reuse
4th lecture RAD 311
15/03/2010

27. RADIONUCLIDE PRODUCTION Preparation of I-131 (carrier free)
target : 2.5g 99+% 130Te
Neutron flux: 2 x 1014n/cm2/sec, 21d
130Te (n,) 131Te  131I
 65 GBq 131I obtained by distillation, as before
130Te recovered for reuse
4th lecture RAD 311
15/03/2010

28. RADIONUCLIDE PRODUCTION Preparation of Mo-99 (non-fission + fission)
target : natural MoO % 98Mo
flux: 2 x 1014n/cm2/sec, 7d
98Mo (n,) 99Mo
 37 GBq 99Mo from 1g MoO3
natural MoO3  185W (T½ = 74d) - absent when enriched 98Mo used
Starting material : 2.5g 93+% 235U
99Mo extracted from acidified solution of fission products
produced in 1000 GBq quantities
high specific activity for generators
may contain some 131I and 103Ru
4th lecture RAD 311
15/03/2010

29. REACTOR PRODUCED RADIONUCLIDES
PRODUCT
DECAY MODE
PRODUCTION REACTION
14C β-
14N(n,p)14C
32P
31P(n,γ)32P
51Cr
EC, γ
50Cr(n,γ)51Cr
59Fe
β-, γ
58Fe(n,γ)59Fe
125I
124Xe(n,γ)125Xe EC I
131I
130Te(n,γ)131Te β I
15/03/2010
4th lecture RAD 311

30. Do we have to have a cyclotron or an accelerator in each hospital
???????

31. Generator
TC99m- Generator
15/03/2010
4th lecture RAD 311

32. 2 Compounds
Parent
Daughter
Long half life
Short half life
Equilibrium

33. RADIONUCLIDE PRODUCTION Radionuclide Generators
allows distribution of short lived nuclides to centres remote from production site
long(er) lived parent nuclide decays to daughter nuclide
allows separation of daughter from parent
separation achieved by difference in chemical properties e.g. charge - ion exchange chromatography
4th lecture RAD 311
15/03/2010

34. RADIONUCLIDE GENERATORS Cross-section of a typical radionuclide generator
4th lecture RAD 311
15/03/2010

35. RADIONUCLIDE GENERATORS Radioactive Decay Laws
common simplifications
T½ parent  10 x T½ daughter
transient equilibrium
e.g. 99Mo / 99Tcm generator h h
4th lecture RAD 311
15/03/2010

36. RADIONUCLIDE GENERATORS Radioactive Decay Laws
common simplifications
T½ parent >> T½ daughter
(p >> d)
secular equilibrium
e.g. 68Ge / 68Ga generator d m
4th lecture RAD 311
15/03/2010

37. RADIONUCLIDE GENERATORS Desirable Properties
ease of operation
daughter should have high chemical and radionuclidic purity
daughter should be a different chemical element to parent
should remain sterile and pyrogen free
daughter should be in a form suitable for preparation of radiopharmaceuticals
4th lecture RAD 311
15/03/2010

38. Technetium Generator Elution
WARNING - PLEASE NOTE:
If using a laptop and projector to display this presentation, the movie MAY not project correctly. It will, however, run OK on the laptop. This problem may be overcome, somewhat inelegantly, by temporarily disabling the display on the laptop display. If this is done (using the keystroke combination applicable for your particular laptop) the movie will then project OK. Simply toggle through the keystroke to display the presentation on both the laptop display and the projector when moving onto the next slide.
The movie is not quite shown in real time. There is about a 1 minute segment removed from the middle of the movie, when the saline is filling the elution vial – rather boring to watch once you’ve grasped what is happening. The entire elution process takes about 3 or 4 minutes in reality. This would normally be done behind thick lead shielding, often in a sterile glove box. However, for the sake of clarity, this elution of an expired generator has been done on a laboratory bench.
15/03/2010
4th lecture RAD 311

39. RADIONUCLIDE GENERATORS Yield Problems
yield is always < 100%
caused by reduced access of eluant to support bed due to -
poor quality ion exchange material
channelling in column during transportation
improper initial packing of column
terminal sterilisation procedures
pseudochannelling - dry vs. wet generators
4th lecture RAD 311
15/03/2010

40. Commonly Used Radionuclides Characteristics
Production Method
Decay Mode
 Emissions (keV)
Half-life
IMAGING
18F
Cyclotron
Positron
511
108 min
67Ga EC
92, 182, 300, 390
78 hr
81Krm
Generator IT
191
13 s
99Tcm
140
6 hr
111In
173, 247
67 hr
123I
160
13 hr
131I
Reactor
Beta
280, 360, 640
8 d
201Tl
68-80
73.5 hr
THERAPY
90Y -
64 hr
186Re
137
90 hr
In Vitro
14C
5760 yr
51Cr
323
27.8 d
125I
27-35
60d
4th lecture RAD 311
15/03/2010

41. Educational Video

42. Assignment
A Mo99m/Tc99m Generator is in transient equilibrium. If the radioactivity of Mo99m at that time is 16 GBq, how much radioactivity of Tc99m will be available 134 hours later if no milking took place during this interval?
Mo99m T1/2= 67 hrs
Tc99m T1/2= 6 hours
4th lecture RAD 311
15/03/2010

43. Thank you
4th lecture RAD 311
15/03/2010