ucl chem2601 imaging l3-4 (nuclear imaging & radiochemistry)

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  • Chem 2601/2011

    Molecular Imaging Lecture 3 and 4: Introduction to Nuclear imaging and Radiochemistry

    Dr. Erik rstad, KLB room 2.11 (e.arstad@ucl.ac.uk)

    1

    mailto:e.arstad@ucl.ac.uk

  • Overview (lecture 3 and 4):

    1) The principles of Nuclear imaging

    2) Nuclear imaging techniques

    3) Instrumentation

    4) Introduction to radioactivity

    5) Production of radionuclides

    6) Radiochemistry

    2

  • Principles of Nuclear Imaging (PET and SPECT)

    O

    HO

    HO

    OH

    HO

    18F

    Tracer, e.g. [18F]FDG

    http://www.hermesmedical.com/showimage.lasso?image_no=283.jpg,575

  • 4

    Nuclear Imaging techniques: 1) Positron emission tomography (PET)

    2) Single Photon Emission Computed Tomography (SPECT)

    3) Autoradiography

  • - Positron: the antimatter equivalent of an electron

    - Positrons are emitted from certain radioactive substances

    - Positrons and electrons annihilates to produce two gamma rays

    Positron

    Electron

    Gamma ray (511 KeV)

    Gamma ray (511 KeV)

  • - A chemical is labelled with a radioactive isotope (positron emitter)

    - Positrons annihilate in surrounding tissue

    - The resulting gamma rays are emitted from the subject

  • Generates 3D maps of radioactivity concentration - tomographic

    http://upload.wikimedia.org/wikipedia/commons/2/25/TomographyPrinciple_Illustration.png

  • Tracer labelled with gamma (single photon) emitting radionuclide

  • 9

    Autoradiography (imaging in vitro):

    Contact exposure of radioactive samples (e.g. 20 m tissue section on X-ray film) Lower resolution than fluorescence microscopy, but quantitative Requires low energy beta emission

    Burton et al. (2009), TOXICOLOGICAL SCIENCES, 111(1): 131139. http://www.nationaldiagnostics.com

  • 10

    Instrumentation: 1) Detector principles

    2) Principle of PET scanners

    3) Principle of SPECT scanners

  • Detector physics and image analysis: From gamma rays to 3D image

    Scintillation detector: Converts gamma rays to light

    Photomultiplier tube (PMT): Converts light to electricity and amplifies signal

    Outgoing amplified signal

  • PET camera: how does it work?

    detector 1

    detector 2

    coincidence window

    time (ns)

  • SPECT camera: how does it work?

    No coincidence detectors are fitted with collimators to filter gamma radiation

  • 14

    Properties of nuclear imaging techniques: (1) Resolution (time and space) +

    (2) Sensitivity +++

    (3) Selectivity +++

    (4) Quantification +++

    (5) Tissue penetration +++

    (6) Invasiveness +++ = non-invasive

    (7) Structural information +

    (8) Functional information +++

    Nuclear imaging enables non-invasive quantitative imaging of biological processes in vivo

  • SPECT vs. PET

    SPECT PET Resolution 12-15mm 4-7mm Sensitivity

    (gamma detection) 0.03% 3.0%

    dual radionuclides yes no Radionuclides Gamma emitters

    half-life > 6 hours Positron emitters

    half-life < 2h Sensitivity

    (Target concentration)

    10-13 molar 10-14 molar

    Cost $$ $$$ (500-2000/scan)

  • Radioactivity: 1) Introduction to radioactivity

    2) Ionizing radiation

    3) Half-life and radioactive decay

    4) Specific activity

    5) Attenuation

    16

  • 17

    What is radioactivity?

  • A brief introduction to Radioactivity:

    1895: Roentgen discovered X-rays 1896: Henri Becquerel discovered rays from uranium

    1897: Marie Curie named the rays radioactivity 1898: Marie and Pierre Curie discovered Polonium and Radium 2012: > 2500 radioactive nuclides are known!

  • 19

    Definitions: A nuclide (from nucleus) is an atomic species characterized by the specific constitution of its nucleus, i.e., by its number of protons Z and its number of neutrons N. A radionuclide is any radioactive nuclide. Isotopes are atoms from the same element (i.e. same proton number) but different number of neutrons.

    18F- Mass number = N + Z Proton (Z) number

    Charge

  • 20

    Radioactivity is defined as the process in which unstable atomic nuclei spontaneously emit ionizing radiation

    Types of ionizing radiation:

    Alpha particles = He nucleus

    Beta particles = electron

    Positrons = antimatter of electrons

    Gamma rays = highly energetic photons

    E = mc2

  • 21

    The units of radioactivity: Historical units: Ci (curie) = 3.7 1010 disintegrations per second (= 1 g of 226Ra) mCi = 37 x 106 disintegrations per second

    SI units: Bq (Becquerel) = 1 disintegration per second KBq = 1 x 103 Bq MBq = 1 x 106 Bq GBq = 1 x 109 Bq Conversion factor: 1 mCi = 37 MBq

  • 22

    Ionizing radiation and energy The energy of ionizing radiation is measured in electron volts (eV) Units: KeV = 1000 eV or MeV = 1000,000 eV For particles it is the kinetic energy (typically 100 KeV to 1 MeV) For gamma rays it is the energy of the photon NB: Gamma energies for SPECT imaging ~ 100-300 KeV For PET the gamma rays are always 511 KeV (the combined mass of an electron and a positron = 1.022 MeV)

  • 23

    At = A0 x e t

    t1/2 = ln 2 / (ln = natural logarithm, ln 2 = 0.693)

    Where n equals number of whole half-lives: At = A0(1/2)n

    Relationship between half-life, time and radioactivity

    The activity of a radioactive sample at any time is:

    The half-life (t1/2) of a radionuclide is determined by its decay constant lambda ():

    Where A0 is the activity at time zero and e = natural constant (2.718)

  • 24

    Half-life and radioactive decay over time

  • Question: Carbon-11 has a half-life of 20 min. The synthesis of a tracer takes 40 min and it takes another 20 min to analyse the product before injection to a subject. The radiochemical yield is 20%. How much of the initial activity is available for injection?

  • 26

    Specific activity: Activity / Mass = Bq / mol

    Direct correlation between half-life and maximum specific activity: t1/2 = ln 2 / is the probability of radioactive decay:

    Low = long t1/2 High = short t1/2 The shorter the half-life the higher the maximum specific activity

  • 27

    Samples exclusively made up of molecules containing the radioactive nuclide are carrier-free (c.f.). Samples without addition of non-radioactive carrier but containing naturally occurring isotopic dilutions are non-carrier-added (n.c.a.). Samples diluted with non-labelled molecules are carrier-added (c.a.).

    Specific activity important terms:

  • Radiation properties: Attenuation

    Range of a couple of cm in air stopped by a sheet of paper

    Range of mm to cm in tissue stopped by a sheet of aluminium

    long range requires thick lead for shielding

    http://upload.wikimedia.org/wikipedia/commons/d/d6/Alfa_beta_gamma_radiation.svg

  • 29

    Attenuation: effect of matter

    http://en.wikibooks.org/wiki/Basic_Physics_of_Nuclear_Medicine/Attenuation_of_Gamma-Rays

    Gamma ray intensity I0 Gamma ray intensity Ix

    0 X

    I = I0 Ix, where I is proportional to Z3 Doubling the atomic number leads to 8 fold increase in attenuation!

  • 30

    Attenuation: effect of matter AND energy

    http://en.wikibooks.org/wiki/Basic_Physics_of_Nuclear_Medicine/Attenuation_of_Gamma-Rays

    Half value (in cm) for gamma rays:

    Biological tissues: Different stopping power of radiation e.g. lungs vs. bones

  • Attenuation of positrons in tissue:

    NB: this defines the maximum theoretical resolution of PET!

  • 32

    Nuclear imaging is quantitative, because: Radioactive decay is determined by the half-life Radioactive decay is unaffected by the environment The interactions of ionizing radiation with matter follows clear physical rules and can be accounted for

  • Question: What would happen if a subject is injected with a PET tracer but scanned with SPECT camera? What would happen if a subject is injected with a SPECT tracer but scanned with PET camera?

  • Radiochemistry: 1) Production of radionuclides

    2) Labelling with 11C

    3) Labelling with 18F

    4) Labelling with 123I

    5) Labelling with 3H

    34

  • 35

    Radiochemistry and production of radionuclides Examples for PET: 11C (t1/2 20.4 min) and 18F (t1/2 110 min) Example for SPECT: 123I (t1/2 13.1 h) Example for autoradiography: 3H (t1/2 12 years)

  • Reaction: Product: half-life: Decay mode:

    16O (p,) 13N 10 min + (positron)

    14N (p,) 11C 20 min + (positron) 14N (d,n) 15O 2 min + (positron) 18O (p,n) 18F 110 min + (positron) 124Te(p,2n) 123I 13.1 h (gamma) 99mTc 6.01 h (gamma) 68Ga 68 min + (positron)

    82Rb 1.26 min + (positron)

    Generator based radionuclides:

    Production of radionuclides with a cyclotron

    36

  • 37

    Production of radionuclides: formation of 3H

    6Li + n

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