Radioactivity, Radionuclide Production

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Radioactivity, Radionuclide Production
Radiopharmaceuticals

• Half-lives and transformations
• Cyclotrons and generators
• Methods of localization

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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

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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

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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

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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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Linear plot of activity versus time
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Semi-logarithmic plot of activity versus 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.

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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

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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

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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

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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

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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

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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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Schematic view of a cyclotron
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Forces from the static magnetic field cause the
ions to travel in a circular path
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Hospital-based cyclotron facility
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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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Fission yield as a percentage of total fission
products from uranium 235
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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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Molybdenum 99/technetium 99m 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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Time-activity curve of a molybdenum 99/technetium
99m radionuclide generator system showing
in-growth of Tc-99m and subsequent elution.
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Clinically used radionuclide generator systems
in nuclear medicine
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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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Time-activity curve demonstrating secular
equilibrium
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Ideal Radiopharmaceuticals

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

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Mechanisms of Localization

• Compartmental localization and leakage
• Cell sequestration
• Phagocytosis
• Passive diffusion
• Metabolism
• Active transport

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Localization (cont.)

• Capillary blockade
• Perfusion
• Chemotaxis
• Antibody-antigen complexation
• Receptor binding
• Physiochemical adsorption