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Cyclotron Selection a. b. c. d. e. Nuclear Reactions Production Methods PET Radionuclides Selection Criteria Radionuclide Production Yield

PET Radionuclides Production Cyclotron Selection and Location

2.

Cyclotron Site a. b. c. Large Vault Design Self-Shielded Option Facility Layout

Carlos Gonzalez Lepera, Ph.D. CYCLOTOPE and Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center Houston, TX

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PET Radionuclides Production a. b. c. Gas Targets Liquid Targets Solid Targets

Displacement Caused by Nuclear Bombardment Reactions

, 3n , 2n n , n , np t, n 3He, p d, p n, t, np n, p t, 3He

Radionuclides Production
Nuclear Reactor Stars Formation Cosmic Rays

3He,

p, n

p, d, n 3He, np Original Nucleus n, n n, d , p n, np n, 3He n, pd

p, t

p, pn , n n, 2n n, t , np d, n, n, n 3He

t, p

Cyclotron

p,

Accelerator

Charged Particle (Accelerator) Neutron Irradiation (Reactor)

Common PET Radioisotopes

Radioisotope
11C 13N

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Principal Nuclear Reactions
14N(p,)11C 16O(p,)13N 14N(d,n)15O 15N(p,n)15O 18O(p,n)18F 20Ne(d, )18F 60Ni(d,n)61Cu 61Ni(p,n)61Cu 63Cu(p,2n)62Zn(9.1

Cyclotron Selection Criteria

Distribution & Research
11C, 13N, 15O, 18F, solid

$
Pre-Clinical Research
11C, 15O, 18F

Half-life 20.3 min 9.96 min 122 sec

Decay (%) + 99.8, EC 0.2 + 100 + 99.9, EC 0.1

Endpoint (MeV) 0.961 1.190 1.723

Purpose

Commercial Distribution
18F

Clinical Research
11C, 13N, 15O, 18F,

Radionuclide

solid ~ 1Ci/batch

15O

Activity

~ 10 Ci/batch

> 1 Ci/batch

< 1 Ci/batch

18F

109.8 min

+ 96.9, EC 3.1

0.635

Particles

H-

H-, D-

H-, D-

H-

61Cu

3.41 hr 9.73 min 12.7 hr 75 sec 14.7 hr 4.15 d

+ 62, EC 38 + 97.8, EC 2.2 + 19, EC 41, - 40 + 96, EC 4 + 34, EC 66 + 25, EC 75

1.205 2.934 0.657 3.35 1.248, others 1.533, 2.134

62Cu

(gen.)

hr) 62Cu

Energy

15 MeV

15 MeV

15 MeV

7 MeV

64Cu 82Rb

64Ni(p,n)64Cu, 64Zn(n,p)64Cu 85Rb(p,4n)82Sr(25 d) 86Sr(p,n)86Y 124Te(p,n)124I

Shielding options:

(gen.)

82Rb

Self + Vault (~30 cm concrete) Vault (~ 200 cm concrete) Long term needs

86Y 124I

Long term investment >10 years

Radionuclide Production Yields

Disintegration Rate: (Activity) D = N . N : Number of atoms A : Probability of decay

Probability of transforming atom A into B

A = ln(2)/T1/2
Batemans equation (balance) for growth of daughter radionuclide B from parent A

Beam I

Target x1 x2

B B = ( A A )

B (1 e ( B A

B A

)t

)
E1 E2

A : Number of target atoms. A: Probability of transforming target atom A into B The product A.A remains finite.

A >> 1 A<<1

A < < B

B B = A A 1 e B t

A = I ( x) dx
x1

x2

A = I

E2

E1

(E ) dE (dE dx)

Radionuclide Production Yield

BB = I (1- e- t) NA / M (E) dE/(dE/dX)

Irradiation Build Up

B B = I 1 e

B t

N A M

E th

Ei

(dE

(E )

dx )

dE
Factor

0.9 0.8 0.7 0.6 06 0.5 0.4 0.3 0.2 0.1 0 0 1 2

Half-life

Yield (mCi)

Saturation Yield (mCi/A)

(I) Beam Current (A) Build-up (irradiation time)

BB = I (1- e- t) NA / M (E) dE/(dE/dX)

BB = I (1- e- t) NA / M (E) dE/(dE/dX)

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O(p,n) F Cross Section

300 250
Saturation Yield (mCi / A)

18

18

O(p,n) F Saturation Yield

18

500

400
Cross Section (mba arn)

300

200 150 100 50

200

100

0 0 5 10
Energy (MeV)

15

20

1 mbarn = 10-27 cm2

10
Energy (MeV)

15

20

Production Efficiency
How many protons per produced 18F atom are needed? 18O(p,n)18F Protons Energy [MeV] Yield* [mCi/A]
18F

Ernest Orlando Lawrence and M. Stanley Livingston

at EOB [mCi]

Protons/18F

10.5 10 5 18

120 200

950 1583

1700 1020

Irradiation conditions : 25 A x 60 min * Typical production yields using >95% enriched 18O-Water

Holifield Radioactive Ion Beam Facility Oak Ridge ,TN

UT Houston Scanditronix MC40

25 MV Terminal

Building

Comparative size for electrostatic accelerator with similar final proton energy as 40 MeV cyclotron

CYCLOTRON MENU
T R I U M F T R 5 0 0 M e V

Sizes:

Small (PET): Medium (SPECT): Large (Therapy):

K(p) < 19 MeV self-shielded option K(p) < 30 MeV vault required K(p) > 30 MeV up to few hundred MeV

Flavors:

Ion Ion Source Magnet Plane Shielding Particles Energy

Positive Internal Conventional Horizontal Self Single Fixed

Negative (p, d only) External Superconducting Vertical Vault Multiple (p,d,,He3) Variable (steps-cont.)

Siemens Eclipse HP GE PETtrace

11 MeV protons 60 A (x2)max. current 16 MeV protons 8 MeV deuterons (option) 60 A max. current

MAX. POWER:

660 W (x2)

MAX. POWER:

960 W

GE PETtrace Self-Shielded

IBA Cyclone 18/9 -HC

18 MeV protons 9 MeV deuterons 150 A max. current

MAX. POWER:

2700 W

ACS TR 19/9
14000
19 MeV protons 9 MeV deuterons >300 A current

Production Capacity
(1 target 2 hours)

12000 10000 F Yie (mCi) eld

100 A 100 A

MAX. POWER:

~ 6000 W

8000 6000 4000 2000 0 0

60 A 60 A 60 A

18

10 Energy (MeV)

15

20

Large Vault (~190 cm walls)

Shielding (neutrons) NCRP 144 Reinforce floor Beam direction Negative pressure Conduits Power and utilities Trenches Product delivery Corner Pit Decay in storage Power supply room Support room Control room Vault door Work bench targets service Product distribution valves

Self-shielded (~30 cm walls)

Shielding (neutrons) NCRP 144 Reinforced floor Beam direction Negative pressure Conduits Power and utilities Trenches Product delivery Corner Pit Decay in storage Power supply room Support room Control room Vault door Work bench targets service Product distribution valves

Target Holder RF Dees

Extractor load lock Open Cyclotron

All parts requiring maintenance can be isolated from the cyclotron vacuum

Beam Lines

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

11C

Nuclear Reaction:

14N

(p,)11C

= 20.3 min

UHP N2

Target Material - Aluminum

beam

N2 + 11CO2

N2 Trapping
11CO 11CO 2

Final Product

Labeling

Purification

Single Dose

Yields

Target : Trapping: Labeling: Purification

~ 1 Ci > 90% ~ 50% ~ 50%

Specific Activity:

1-10 Ci/mol (10-3)

Commercial Distribution: NO

13N

Nuclear Reaction:

16O

(p,)13N

= 9.96 min

15O

Nuclear Reaction:

14N

(d,n)15O

= 2.03 min

He gas (500 psi)

Target Material - Aluminum

Water Cooling

UHP N2 +5% H2

beam H2O + EtOH (trace)

Target Material - Aluminum

beam

N2 + H215O

N2
Final Product
13N-Ammonia

Trapping Conversion Purification

Conversion

Final

H215O C [15O] O [15O]

H2

15O

Product

Purification

Single/Dual Dose

Purification

Single Dose

Yields

Target : Labeling: Purification

500 mCi In target ~ 95%

Specific Activity:

NCA

Yields

Commercial Distribution: Very Limited

Target : Trapping: Conversion: Purification

500 mCi ~ 80% ~ 40-80% ~ 98%

Specific Activity:

NA

Commercial Distribution: NO

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18F

Nuclear Reaction:

18O

(p,n)18F
He gas (500 psi)

= 109.8 min

61Cu

Nuclear Reaction:

60Ni

(d,n)61Cu - nat.Ni : 60Ni (26.1%)

= 3.41 hr

Beam Power > 6 kW

Target Holder Material - Titanium - Silver - Niobium - Tantalum

Water Cooling

> 1 kW Power Dissipation!

Target Material - Aluminum

beam
Water Cooling

beam

H218O ( > 95%)

H218O recover
Synthesis Unit
18F

K222 + K2CO3

Ni waste/recover Ion Exchange Resin

T ~ 90 C HCl Target Dissolving Final Product BATCH

Precursor Reaction Vessel

18F

trap

Final Product Purification Batch

H2O/HCl

Yields

Target : Trapping: Labeling: Purification

5-10 Ci > 95% 30-60% ~ 95%

Specific Activity:

NCA

Yields

Commercial Distribution: YES !

Target : Trapping: Labeling: Tracers:

100 mCi > 98% 30-80% 61Cu-ATSM Cu-

Specific Activity:

NCA

Commercial Distribution: YES

124I

Nuclear Reaction:

124Te

(p,n)124I

124TeO

2/Al2O3

= 4.4 d

Platinum or Tantalum substrate Target Material - Aluminum

beam
Water Cooling

Class 100 Mini Cells

T ~ 670 C NaOH Trap H2O Dry Distillation O2 Final Product BATCH

Yields

Target : Trapping: Labeling: Tracers:

200 mCi ~ 80% ~50% 124I-mab/FIAU

Specific Activity:

> 30 Ci/mol

Commercial Distribution: YES

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Dual FDG Production Units

Laminar Flow Dispensing Hot Cell

Dose Dispensing

FDA Approved:
18F[NaF] 18F[FDG] 13N-Ammonia 82Rb

Potential New Tracers

F18-Acetate F18-Fluorodopa F18-FLT C11 PIB C11 Acetate C11 Palmitate C11 Tracers I124 MoAb Cu-61/64 ATSM Zn62/Cu62 Generator

Primary Application
Oncology/Cardiology Neurology -Oncology Oncology DNA marker Cell Proliferation Detection Alzheimers disease (F18) Heart/Prostate Fatty Acid Metab Heart Brain Receptors Oncology/Diag.-Treatment Hypoxia Heart

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FDG

Fluoroacetate

Thank you y

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