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Radioactivity, Radionuclide Production

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Title: Radioactivity, Radionuclide Production


1
Radioactivity, Radionuclide Production
Radiopharmaceuticals
  • Half-lives and transformations
  • Cyclotrons and generators
  • Methods of localization

2
Activity
  • The quantity of radioactive material, expressed
    as the number of radioactive atoms undergoing
    nuclear transformation per unit time, is called
    activity (A)
  • Traditionally expressed in units of curies (Ci),
    where 1 Ci 3.70 x 1010 disintegrations per
    second (dps)
  • The SI unit is the becquerel (Bq)
  • 1 mCi 37 MBq

3
Decay Constant
  • Number of atoms decaying per unit time is
    proportional to the number of unstable atoms
  • Constant of proportionality is the decay constant
    (?)
  • -dN/dt ? N
  • A ? N

4
Physical Half-Life
  • Useful parameter related to the decay constant
    defined as the time required for the number of
    radioactive atoms in a sample to decrease by one
    half
  • ? ln 2/Tp1/2 0.693/Tp1/2
  • Physical half-life and decay constant are
    inversely related and unique for each radionuclide

5
Fundamental Decay Equation
  • Nt N0e-?t or At A0e-?t
  • where
  • Nt number of radioactive atoms at time t
  • At activity at time t
  • N0 initial number of radioactive atoms
  • A0 initial activity
  • e base of natural logarithm 2.71828
  • decay constant ln 2/Tp1/2 0.693/Tp1/2
  • t time

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Nuclear Transformation
  • When the atomic nucleus undergoes spontaneous
    transformation, called radioactive decay,
    radiation is emitted
  • If the daughter nucleus is stable, this
    spontaneous transformation ends
  • If the daughter is unstable, the process
    continues until a stable nuclide is reached
  • Most radionuclides decay in one or more of the
    following ways (a) alpha decay, (b) beta-minus
    emission, (c) beta-plus (positron) emission, (d)
    electron capture, or (e) isomeric transition.

9
Alpha Decay
  • Alpha (?) decay is the spontaneous emission of an
    alpha particle (identical to a helium nucleus)
    from the nucleus
  • Typically occurs with heavy nuclides (A gt 150)
    and is often followed by gamma and characteristic
    x-ray emission

10
Beta-Minus (Negatron) Decay
  • Beta-minus (?-) decay characteristically occurs
    with radionuclides that have an excess number of
    neutrons compared with the number of protons
    (i.e., high N/Z ratio)
  • Any excess energy in the nucleus after beta decay
    is emitted as gamma rays, internal conversion
    electrons or other associated radiations

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Beta-Plus Decay (Positron Emission)
  • Beta-plus (?) decay characteristically occurs
    with radionuclides that are neutron poor (i.e.,
    low N/Z ratio)
  • Eventual fate of positron is to annihilate with
    its antiparticle (an electron), yielding two
    511-keV photons emitted in opposite directions

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Electron Capture Decay
  • Alternative to positron decay for
    neutron-deficient radionuclides
  • Nucleus captures an orbital (usually K- or
    L-shell) electron
  • Electron capture radionuclides used in medical
    imaging decay to atoms in excited states that
    subsequently emit detectable gamma rays

15
Isomeric Transition
  • During radioactive decay, a daughter may be
    formed in an excited state
  • Gamma rays are emitted as the daughter nucleus
    transitions from the excited state to a
    lower-energy state
  • Some excited states may have a half-lives ranging
    up to more than 600 years

16
Decay Schemes
  • Each radionuclides decay process is a unique
    characteristic of that radionuclide
  • Majority of pertinent information about the decay
    process and its associated radiation can be
    summarized in a line diagram called a decay
    scheme
  • Decay schemes identify the parent, daughter, mode
    of decay, intermediate excited states, energy
    levels, radiation emissions, and sometimes
    physical half-life

17
Generalized Decay Scheme
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Radionuclide Production
  • All radionuclides commonly administered to
    patients in nuclear medicine are artificially
    produced
  • Most are produced by cyclotrons, nuclear
    reactors, or radionuclide generators

24
Cyclotrons
  • Cyclotrons produce radionuclides by bombarding
    stable nuclei with high-energy charged particles
  • Most cyclotron-produced radionuclides are neutron
    poor and therefore decay by positron emission or
    electron capture
  • Specialized hospital-based cyclotrons have been
    developed to produce positron-emitting
    radionuclides for positron emission tomography
    (PET)
  • Usually located near the PET imager because of
    short half-lives of the radionuclides produced

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Nuclear Reactors
  • Specialized nuclear reactors used to produce
    clinically useful radionuclides from fission
    products or neutron activation of stable target
    material
  • Uranium-235 fission products can be chemically
    separated from other fission products with
    essentially no stable isotopes (carrier) of the
    radionuclide present
  • Concentration of these carrier-free
    fission-produced radionuclides is very high

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Neutron Activation
  • Neutrons produced by the fission of uranium in a
    nuclear reactor can be used to create
    radionuclides by bombarding stable target
    material placed in the reactor
  • Process involves capture of neutrons by stable
    nuclei
  • Almost all radionuclides produced by neutron
    activation decay by beta-minus particle emission

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Radionuclide Generators
  • Technetium-99m has been the most important
    radionuclide used in nuclear medicine
  • Short half-life (6 hours) makes it impractical to
    store even a weekly supply
  • Supply problem overcome by obtaining parent
    Mo-99, which has a longer half-life (67 hours)
    and continually produces Tc-99m
  • A system for holding the parent in such a way
    that the daughter can be easily separated for
    clinical use is called a radionuclide generator

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Transient Equilibrium
  • Between elutions, the daughter (Tc-99m) builds up
    as the parent (Mo-99) continues to decay
  • After approximately 23 hours the Tc-99m activity
    reaches a maximum, at which time the production
    rate and the decay rate are equal and the parent
    and daughter are said to be in transient
    equilibrium
  • Once transient equilibrium has been reached, the
    daughter activity decreases, with an apparent
    half-life equal to the half-life of the parent
  • Transient equilibrium occurs when the half-life
    of the parent is greater than that of the
    daughter by a factor of 10

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Secular Equilibrium
  • If the half-life of the parent is very much
    longer than that of the daughter (I.e., more than
    about 100? longer), secular equilibrium occurs
    after approximately five to six half-lives of the
    daughter
  • In secular equilibrium, the activity of the
    parent and the daughter are the same if all of
    the parent atoms decay directly to the daughter
  • Once secular equilibrium is reached, the daughter
    will have an apparent half-life equal to that of
    the parent

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Ideal Radiopharmaceuticals
  • Low radiation dose
  • High target/nontarget activity
  • Safety
  • Convenience
  • Cost-effectiveness

41
Mechanisms of Localization
  • Compartmental localization and leakage
  • Cell sequestration
  • Phagocytosis
  • Passive diffusion
  • Metabolism
  • Active transport

42
Localization (cont.)
  • Capillary blockade
  • Perfusion
  • Chemotaxis
  • Antibody-antigen complexation
  • Receptor binding
  • Physiochemical adsorption
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