prof. dr. s. i. ziegler technology in nuclear...

Technische Universität München

Nuklearmedizinische Klinik und PoliklinikKlinikum rechts der Isar Technische Universität München

Nuklearmedizinische Klinik und PoliklinikKlinikum rechts der Isar Technische Universität MünchenTechnische Universität München

Technology in Nuclear Medicine

Prof. Dr. S. I. Ziegler

Winter Term 2010/2011



Nuklearmedizinische Klinik und PoliklinikKlinikum rechts der Isar

Outline of the Lecture

1. Date Principles of Nuclear Medicine, Radionuclides

2. Date Interaction of Radiation with Matter, Detectors

3. Date Gamma Camera, SPECT Technology

4. Date Development of Gamma Camera/SPECT

5. Date PET Equipment Technology

6. Date Tools for High Resolution PET

7. Date Image Reconstruction

8. Date Quantification

9. Date PET/CT Dual Modality Tomography

10. Date Nuclear Medical Applications

11. Date Tour of Nuklearmedizin MRI

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Principles of Nuclear Medicine




Aims of Nuclear Medicine

• Diagnostics

Visualisation and quantification of biochemical processes in vivo

• Therapy:

Treatment of pathologic processes based on selective accumulation in body tissues

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Principles of Nuclear Medical Diagnostics

• Tracer principle

Radiopharmaceuticals are distributed, metabolized or excreted in

the organism according to their structure

• Representation of body functions by:

– Images

– Numerical data

– Graphs

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Non-invasive examination of physiological processes




Radiopharmaceuticals

• Selection of the pharmaceutical according to the organ-specific question

• Labelling of pharmaceuticals with radioactive isotopes

External detection possible

• Radiopharmaceuticals must not affect the metabolism

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Nuclear Medical Examinations

Tracer principle

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Non-invasive observation of physiological processes




Types of Radiation – Range in Tissue

Energy Range

α some MeV < 1mm

β 100 keV – 1MeV ~ some mm

γ 100 keV – 500 keV < some cm

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Isotopes for Nuclear Medical Imaging

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Nuclide Half Life TypeEnergy (keV)

99mTc 6 h γ 140

201Tl 73 h γ 70

123I 13 h γ 159

131I 8 d γ 364

18F 110 min e+, γγ 511




Target Structures in Oncology

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FDG

Choline

Antibodies

Peptide Receptors

TK

Receptors Transporters

HSV-TkAcetate

Nucleosides

Nucleosides

O2

Local Concentration

Local Concentration

PeptidesPS

Amine Precursors

Hypoxia

Apoptosis

Amino Acids

Transport, Protein Synthesis

Transport, Choline Kinase

Integrin Expression,Neovascularization

Antigen Expression

Transport, Hexokinase

Lipid Synthesis

APUD-System

Neuropep. ReceptorsMonitoring Gene Expression

Proliferation

Inhibitors

Growth Factor Receptors




Mechanisms of Tracer Imaging

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Mechanism Example

Distribution in a body compartment Blood pool scintigraphy, cystography

Leaking from the vascular compartment

Gastrointestinal bleeding

Passive diffusion Distribution in the tissue along a concentration gradient

Capillaries blocking Lung perfusion scintigraphy (Tracer Ø > 20 µm)

Adsorption Skeleton scintigraphy (Tc-99m-diphosponates on the surface of hydroxylapatite)

Active transport Thyroid scintigraphy, MIBG-scintigraphy, FDG - and AS-PET

Metabolic trapping FDG in cell because of selective blocking of glucose

Phagocytosis Liver, spleen and bone marrow scintigraphy Ø < 10µm

Receptor bond Selective binding of ligands and receptors e.g. in tumours and brain

Antigen- antibody reaction Radioimmunoscintigraphy




Examples for Nuclear Medical Examinations




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131I – Scintigraphy

metastatic thyroid carcinoma




03.12.2010 1499mTc MDP Bone Scan




Glucose Metabolism in the Brain

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Surface Projections

Early Alzheimer Disease Typical Alzheimer Disease

von rechts

Normal Person

right left

100%

0%




FDG PET of a Normal Person

Brain

Kidney

Bladder

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Nuklearmedizinische Klinik und PoliklinikKlinikum rechts der IsarFDG PET: Metastases from Colon

Carcinoma

Thyroid

Mediastinum

Scapula

Liver

Projection Axial Slices03.12.2010 17




Tomography SPECT Recording

Gamma Camera

Gamma Camerameasures projections of activity distribution Spatial Resolution

clinical: ~8 – 20 mm

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SPECT: Single Photon Emission Computed Tomography




Coincidence circuit

PET Measuring Principle

Electronic Collimation

γ

γ

(511 keV)

(511 keV)

Nucleus

e+

e-

180±0.25°

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Radionuclides




PET Nuclides

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Nuclide Half life

(min)

Most common Energy (MeV)

Maximal Range(mm)

Average Range(mm)

15O 2,1 0,696 8,22 1,49

13N 10 0,432 5,35 1,42

11C 20,3 0,326 4,98 1,11

18F 109,7 0,205 2,39 1,02




PET Tracer Methode - Advantages

• High sensitivity (pmol)

• High specificity (molecular targeting)

• Biologic active substance (11C, 18F)

• No Influence of the investigated process

• No toxic effect

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Conditions for Nuclear Medicine

Gamma emitter with short to very short physical half life

Technical imaging properties: � Tc-99m

“Biologic labelling”: e+ emitter

Radio nuclides have to be produced

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Generator system

short T1/2

Isomerlong T1/2

β+, β-, EC

Reactor, Accelerator

parent nuclide

daughter nuclide

end product

Radio Nuclide Generator

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stable




Decay rate of parent nuclide:

Decay rate of daughter nuclide:

Daughter activity:

Daughter with a much shorter decay time:

pp

pN

dt

dNλ−=

ddppd NN

dt

dNλ−λ=

( )( )t

pd

dppdd

pde1NNλ−λ−

−λ−λ

λλ=λ

( )t

ppddde1NN λ−−λ=λ

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Generator – Transient Equilibrium

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T 1/2

6 h

66 h

Branching ratio = 1




Generator – Secular Equilibrium

Branching ratio = 1

T 1/2

15,4 d

5 sec

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Radio Nuclide Generators

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Parent T1/2 Decay Daughter T1/2 Decay Product

99Mo 66,02 h β- 99mTc 6,02 h isomer 99Tc

188W 69,4 d β- 188Re 16,9 h β- 188Os

68Ge 288 d EC 68Ga 68,3 min β+, EC 68Zn

82Sr 25 d EC 82Rb 1,25 min β+, EC 82Kr




Decay Scheme 99Mo over 99mTc to 99Tc

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http://www5.atpages.jp/~rad/index.php?Mo-99

235U(n,fission)99Mo




Al2O3

NaCl

99mTcO4-

MoO42-

Tc-99m Generator




Tc-99m Generator

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Positron Emitter

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Nuclide T1/2

Nuclear Reaction

Target Material

18F 109,7min18O(p,n)18F

20Ne(d, α)18F

18O-water

Ne vapour

11C 20,4 min 14N(p, α)11C N2 vapour

13N 9,96 min 16O(p, α)13N water

15O 2,07 min 15N(p,n)15O enriched gas




Nuclear Reactions

• Reaction cross section σ reaction probability

[σ] = 1 barn = 10-28 m2

• Depends on Radiation type

Energy

• Reaction rate: R = σ F n V

F: particle flux density

n: atomic number density

V: target volume

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Nuclear Reactions – Cross section

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Nuclear Reactions

• Reaction rate: R = σ F n V

Product is radioactive with decay constant λ

• Netto production: dN(t) = Rdt - λN(t)dt

• Product activity: A(t) = R(1 - exp(-λt))

R: maximal achievable activity (saturation activity)

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“Dees”

Ion source

Extraction

Cyclotron – Principle

Homogeneous magnetic field B perpendicular to plane of projection

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• Ions with charge ze, initial speed v0

• Within magnetic field B: Lorentz force

• Centrifugal force = Lorentz force

r = path radius

Momentum p0 = m v0 = ze B r

Circular frequency ωωωω: v = ω r

• ωωωω is independent of radius or velocity

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BvezF 0L ⋅= pathparticleFL ⊥

Bv ze r

v m 0

20 =

m

Bze=ω





• High frequency voltage applied on “Dees” alternating with ω

Particles are accelerated at each rotation

• Kinetic Energy

Maximum energy depends of z2/2m

therefore protons get higher energy as deuterons

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( )m2

rBze

rBze2

1vrBze

2

1mv

2

1E

2

22K

=

=ω===




-

NegativeIons

+

-

-

-

+

Target

Trajectoryat 11 MeV

Carbon foilProton

Cyclotron – Negative Ions

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Cyclotron for PET-Nuclides

40




Nuklear-medizinTUM

Targets – RDS112

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Nuklear-medizinTUM

Synthesis Device

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Cyclotron – CTI/Siemens RDS112

• Diameter ~ 1 m

• Maximum energy: 11 MeV

• Dees: voltage 16 kV, 27 MHz

• Ion current on target: max. 40 µA

• Max. achievable activity:

11C 70 GBq

13N 10 GBq

15O 100 GBq

18F 70 GBq

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