1.
PET Radionuclides Production
a.
b.
c.
d.
e.
Cyclotron Selection and Location
2.
Carlos Gonzalez Lepera, Ph.D.
CYCLOTOPE and
Experimental Diagnostic Imaging,
The University of Texas MD Anderson Cancer Center
Houston, TX
Cyclotron Selection
Cyclotron Site
a.
b.
c.
3.
α, 2n
n
α, n
p, n
p, γ
d, n
3He, np
α, np
t, n
3He, p
p, t
p, pn
γ, n
n, 2n
Original
Nucleus
n, n
d, p
n, γ
t, np
p,α
n, t
γ, np
d, α
n, d
γ, p
n, np
n, p
t, 3He
n, α
n, n 3He
n, 3He
n, pd
Gas Targets
Liquid Targets
Solid Targets
Radionuclides
Production
Displacement Caused by Nuclear
Bombardment Reactions
3He,
Large Vault Design
Self-Shielded Option
Facility Layout
PET Radionuclides Production
a.
b.
c.
α, 3n
Nuclear Reactions
Production Methods
PET Radionuclides
Selection Criteria
Radionuclide Production Yield
Nuclear Reactor
Stars Formation
Cosmic Rays
t, p
Cyclotron
Accelerator
Charged Particle (Accelerator)
p
Neutron Irradiation (Reactor)
n
1
$
Common PET Radioisotopes
β+
Radioisotope
Half-life
Decay (%)
11C
20.3 min
β+ 99.8, EC 0.2
0.961
14N(p,α)11C
13N
9.96 min
β+ 100
1.190
16O(p,α)13N
15O
122 sec
18F
109.8 min
β+
Endpoint (MeV)
99.9, EC 0.1
1.723
β+ 96.9, EC 3.1
0.635
Principal Nuclear Reactions
2.934
12.7 hr
β+ 19, EC 41, β- 40
0.657
75 sec
β+ 96, EC 4
3.35
86Y
14.7 hr
β+ 34, EC 66
1.248, others
86Sr(p,n)86Y
124I
4.15 d
β+ 25, EC 75
1.533, 2.134
124Te(p,n)124I
(gen.)
Activity
20Ne(d, α)18F
β+ 97.8, EC 2.2
82Rb
~ 10 Ci/batch
> 1 Ci/batch
~ 1Ci/batch
< 1 Ci/batch
H-
H-, D-
H-, D-
H-
Energy
≥ 15 MeV
≥ 15 MeV
≥ 15 MeV
≥ 7 MeV
61Ni(p,n)61Cu
63Cu(p,2n)62Zn(9.1
hr) → 62Cu
64Ni(p,n)64Cu, 64Zn(n,p)64Cu
85Rb(p,4n)82Sr(25 d)
Shielding options:
Self + Vault (~30 cm concrete)
Vault (~ 200 cm concrete)
→ 82Rb
Long term needs
Long term investment >10 years
N : Number of atoms
λA : Probability of decay
Beam
λA = ln(2)/T1/2
λB
(1 − e −(λ
λB − λ A
A : Number of target atoms.
λA: Probability of transforming target atom A into B
The product A.λA remains finite.
(
B −λ A
)
E1
A >> 1
λA<<1
B ⋅ λB = A ⋅ λ A 1 − e − λB ⋅t
)⋅t
Target
x1 x2
I
Bateman’s equation (balance) for growth of daughter radionuclide B from parent A
λA < < λB ⇒
11C, 15O, 18F
Probability of transforming atom A into B
D = N . λΑ
B ⋅ λB = ( A ⋅ λ A )
solid
Particles
Radionuclide Production Yields
Disintegration Rate:
(Activity)
11C, 13N, 15O, 18F,
Pre-Clinical
Research
60Ni(d,n)61Cu
9.73 min
64Cu
11C, 13N, 15O, 18F,
solid
Clinical Research
18O(p,n)18F
1.205
(gen.)
Distribution &
Research
18F
Radionuclide
15N(p,n)15O
β+ 62, EC 38
62Cu
Commercial
Distribution
14N(d,n)15O
3.41 hr
61Cu
Purpose
$
Cyclotron Selection Criteria
)
x2
λA = I ⋅ ∑σ ( x) ⋅ dx
x1
E2
⇒
λA = I ⋅ ∫
E2
E1
σ (E )
⋅ dE
(dE dx)
2
BλB = I (1- e-λ t) NAρ / M σ(E)
dE/(dE/dX)
Β
Radionuclide Production Yield
Irradiation Build Up
(
)
N ⋅ρ
⋅ A
⋅
M
E th
σ (E )
∫ (dE
Ei
dx )
1
0.9
dE
0.8
0.7
Factor
B ⋅ λB = I 1 − e
− λ B ⋅t
Yield (mCi)
06
0.6
0.5
0.4
Saturation Yield (mCi/μA)
0.3
(I) Beam Current (μA)
0.2
0.1
Build-up (irradiation time)
0
0
1
2
3
4
5
Half-life
BλB = I (1- e-λ t) NAρ / M σ(E)
dE/(dE/dX)
BλB = I (1- e-λ t) NAρ / M σ(E)
dE/(dE/dX)
Β
18
Β
18
18
18
O(p,n) F Saturation Yield
500
300
400
250
Saturation Yield (mCi / μA)
Cross Section (mba
arn)
O(p,n) F Cross Section
300
200
100
200
150
100
50
0
0
5
10
Energy (MeV)
15
0
20
1 mbarn = 10-27 cm2
0
5
10
15
20
Energy (MeV)
3
Ernest Orlando Lawrence and M. Stanley Livingston
Production Efficiency
How many protons per produced 18F atom are needed?
18O(p,n)18F
18F
Protons/18F
Protons Energy
[MeV]
Yield*
[mCi/μA]
at EOB
[mCi]
10 5
10.5
120
950
1700
18
200
1583
1020
Irradiation conditions : 25 μA x 60 min
* Typical production yields using >95% enriched 18O-Water
Holifield Radioactive Ion Beam Facility – Oak Ridge ,TN
25 MV Terminal
UT Houston – Scanditronix MC40
Building
Comparative size for electrostatic accelerator with
similar final proton energy as 40 MeV cyclotron
4
CYCLOTRON MENU
T
R
I
U
M
F
Sizes:
T
R
Flavors:
5
0
0
M
e
V
Small (PET):
K(p) < 19 MeV self-shielded option
Medium (SPECT):
K(p) < 30 MeV vault required
Large (Therapy):
K(p) > 30 MeV up to few hundred MeV
Ion
Positive
Negative (p, d only)
Ion Source
Internal
External
Magnet
Conventional
Superconducting
Plane
Horizontal
Vertical
Shielding
Self
Vault
Particles
Single
Multiple (p,d,α,He3)
Energy
Fixed
Variable (steps-cont.)
Siemens Eclipse HP
GE PETtrace
11 MeV protons
60 μA (x2)max. current
MAX. POWER:
660 W (x2)
16 MeV protons
8 MeV deuterons (option)
60 μA max. current
MAX. POWER:
960 W
5
IBA Cyclone® 18/9 -HC
GE PETtrace Self-Shielded
18 MeV protons
9 MeV deuterons
150 μA max. current
MAX. POWER:
ACS TR 19/9
2700 W
Production Capacity
(1 target – 2 hours)
14000
19 MeV protons
9 MeV deuterons
12000
>300 μA current
100 μA
100 μA
8000
6000
18
~ 6000 W
F Yieeld (mCi)
10000
MAX. POWER:
60 μA
4000
60 μA
2000
60 μA
0
0
5
10
15
20
Energy (MeV)
6
Large Vault (~190 cm walls)
Self-shielded (~30 cm walls)
Shielding (neutrons)
Shielding (neutrons)
NCRP 144
NCRP 144
Reinforce floor
Reinforced floor
Beam direction
Beam direction
Negative pressure
Negative pressure
Conduits – Power and utilities
Conduits – Power and utilities
Trenches – Product delivery
Trenches – Product delivery
Corner Pit – Decay in storage
Corner Pit – Decay in storage
Power supply room
Power supply room
Support room
Support room
Control room – Vault door
Control room – Vault door
Work bench – targets service
Work bench – targets service
Product distribution valves
Product distribution valves
Target Holder
RF Dees
Extractor
load lock
Open Cyclotron
All parts requiring maintenance can be isolated from the cyclotron vacuum
7
Beam Lines
8
Extraction Foil
Target holder accepts
four targets on either
side of cyclotron into
vacuum sealed mount.
Target Holder mounted
to cyclotron. Positioned
with mechanical bellows
adjustment
9
11C
Nuclear Reaction:
14N
τ = 20.3 min
(p,α)11C
UHP N2
Target Material
- Aluminum
N2 + 11CO2
beam
N2
Trapping
11CO
2
Final Product
11CO
Labeling
Yields
13N
Nuclear Reaction:
16O
τ = 9.96 min
(p,α)13N
Target :
Trapping:
Labeling:
Purification
15O
2
~ 1 Ci
> 90%
~ 50%
~ 50%
Nuclear Reaction:
Purification
Single Dose
Specific Activity:
1-10 Ci/μmol (10-3)
Commercial Distribution: NO
14N
He gas (500 psi)
Target Material
- Aluminum
Water Cooling
UHP N2 +5% H2
Target Material
- Aluminum
beam
τ = 2.03 min
(d,n)15O
N2 + H215O
beam
H2O + EtOH (trace)
N2
Final Product
13N-Ammonia
Purification
Yields
Target :
Labeling:
Purification
500 mCi
In target
~ 95%
Specific Activity:
Final
Trapping
Conversion
Conversion
H2
15O
Product
H215O
C [15O]
O [15O]
Purification
Purification
Single/Dual Dose
NCA
Commercial Distribution: Very Limited
Yields
Target :
Trapping:
Conversion:
Purification
500 mCi
~ 80%
~ 40-80%
~ 98%
Specific Activity:
Single Dose
NA
Commercial Distribution: NO
10
18F
18O
Nuclear Reaction:
τ = 109.8 min
(p,n)18F
61Cu
Nuclear Reaction:
60Ni
(d,n)61Cu - nat.Ni : 60Ni (26.1%)
τ = 3.41 hr
He gas (500 psi)
Beam Power > 6 kW
Target Holder Material
- Titanium
- Silver
- Niobium
- Tantalum
> 1 kW Power Dissipation!
Water Cooling
beam
Target Material
- Aluminum
beam
H218O ( > 95%)
H218O recover
Water Cooling
T ~ 90 ºC HCl
Ni waste/recover
K222 + K2CO3
Synthesis
18F
Precursor
Unit
trap
Ion Exchange Resin
18F
Reaction
Vessel
Yields
Target :
Trapping:
Labeling:
Purification
124I
Final Product
Purification
5-10 Ci
> 95%
30-60%
~ 95%
Nuclear Reaction:
124TeO
NCA
2/Al2O3
BATCH
Yields
Commercial Distribution: YES !
(p,n)124I
Final Product
Batch
Specific Activity:
124Te
Target Dissolving
H2O/HCl
τ = 4.4 d
Platinum or Tantalum substrate
Target :
Trapping:
Labeling:
Tracers:
100 mCi
> 98%
30-80%
61Cu
Cu--ATSM
Specific Activity:
NCA
Commercial Distribution: YES
Class 100
Mini Cells
Target Material
- Aluminum
beam
Water Cooling
T ~ 670 ºC
Dry
Distillation
NaOH Trap
H2O
O2
Final Product
BATCH
Yields
Target :
Trapping:
Labeling:
Tracers:
200 mCi
~ 80%
~50%
124I-mab/FIAU
Specific Activity:
> 30 Ci/μmol
Commercial Distribution: YES
11
Dual FDG Production Units
Laminar Flow Dispensing Hot Cell
Dose Dispensing
FDA Approved:
Potential New Tracers
Primary Application
F18-Acetate
Oncology/Cardiology
18F[NaF]
F18-Fluorodopa
Neurology -Oncology
18F[FDG]
F18-FLT
Oncology –DNA marker –Cell
Proliferation
13N-Ammonia
C11 – PIB
Detection Alzheimer’s disease (F18)
82Rb
C11 – Acetate
Heart/Prostate
C11 – Palmitate
Fatty Acid Metab – Heart
C11 – Tracers
Brain Receptors
I124 – MoAb
Oncology/Diag.-Treatment
Cu-61/64 ATSM
Hypoxia
Zn62/Cu62 Generator
Heart
12
FDG
Fluoroacetate
Thank you
y
13