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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 activitye = 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.
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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 > 150) and is often followed by gamma and characteristic x-ray emission
energyn transitioHe YX 242
4A2Z
AZ
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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
energy β YX -A1Z
AZ
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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
energy β YX A1-Z
AZ
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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
energy Y e X A1-Z
-AZ
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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
energy X X AZ
AmZ
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Decay Schemes
• Each radionuclide’s 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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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
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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