Transcript Radiation Biology 2010 Slides

Introductory Radiation Biology
Lecture 1: August 24, 2010.
Dr. Michael R. Lewis, Associate Professor
Veterinary Medicine & Surgery/Radiology/NSEI
Room F007, HSTMVH Research Service
814-6000 ext 53703, Office hours by Appt. Only
[email protected]
Texts:
Radiobiology for the Radiologist, Eric J. Hall
Mizzou Media Handount Book
Reading Assignments:
Handout: Chapters 1-4, Handout .99
Hall: Chapters 1 and 7 (First 2 sections)
For Radiation Biology, our main interest is in the
biological effects of ionizing radiation produced by
artificial sources or radioactive decay processes.
Many of you will be working with radiation sources
and/or radioactive materials as a profession. It is
essential that you understand not only the
biological effects of radiation, but also the
physical interactions of radiation with matter
(which by in part give rise to the biological
effects).
Some radiations are more hazardous to one’s
health than others, hence the reasoning for this
understanding.
The Hazards from Ionizing Radiation Depend
On the Following:
1. The type of radiation.
2. The mode of decay of the radionuclide.
3. The half-life of the radionuclide.
4. The biological handling of the radionuclide.
The History of Radiation Sciences/Radiobiology:
1. December 28 1895, Wilhelm Conrad Rontgen: Discovered a “new
kind of ray” emitted from gas discharge tubes that blackened
photographic plates in light-tight containers. He called them Xrays because of their unknown nature.
When his work was complete, X-rays were very well-characterized;
he won the 1901 Nobel Prize in Physics for this discovery.
2. January 1896: Rontgen produced the first radiograph of a human
hand. The first medical use of X-rays were to locate and remove a
piece of knife blade from the backbone of a drunken sailor.
3. 1896, Henri Becquerel: Showed the existence of naturally-occuring
radiaiton in uranyl sulfate; he won the 1903 Nobel Prize in Physics.
4. 1898, Pierre & Marie Curie: Concluded that uranium rays are an
atomic phenomenon characteristic of the element and not related
to it’s chemical or physical state. They named it “radioactivity” and
shared the 1903 Nobel Prize in Physics with Becquerel. The
Curies isolated Po & Rad from a ton of pitchblende and Marie won
the 1911 Nobel Prize in Chemistry for discovery of these elements
(Pierre had died in 1906 in a carriage accident).
Early Biological Effects of Radiation:
1. April 1896, Daniels: Daniels, a physician at Vanderbilt University,
demonstrated the first biological effect of ionizing radiation (the
epilation of scalp after X-irradiation of the skull).
2. 1897: Freund removed a hairy birthmark, considered to be the first
therapeutic use of X-rays.
3. 1899, First Tumor Therapy: Stenbeck & Sjogren in Sweden
removed a skin tumor from the tip of a patient’s nose with X-rays.
4. 1903, Senn: In Chicago, reduced the spleen sized of leukemic
patient with X-rays.
Early Harmful Effects of Radiation:
1. Henri Becquerel: Becquerel used to carry a radium vial in his vest
pocket for demonstrations. He noticed a reddening of the skin
(erythema) in this area and the subsequent development of an
ulcer. Pierre Curie reproduced this experiment in 1901 by
deliberately producing a radium burn on his forearm, charting the
appearance and healing of the radiation ulcer. Thus, the field of
Radiobiology was born.
Harmful effects became obvious by the early 1900s, but went
unattended for many years.
2. Latent Cancer: Both Marie & Irene Curie died of leukemia at an
advanced age, probably the result of exposure to high levels of
radioactivity.
3. Mutation: H. J. Muller (1927) demonstrated that ionizing radiation
produced genetic mutations in the fruit fly Drosophila. L.J. Stadler
(MU) showed the same effect in maize. Muller published ~2
months earlier than Stadler and was awarded the 1946 Nobel Prize
in Physiology/Medicine.
Radiation Energetics:
Two Classes of High Energy Radiation:
1. Particulate Radiation.
2. Electromagnetic Radiation.
Properties of Particulate Radiation:
1. Mass: Particles are composed of matter. Particles have mass.
2. Kinetic Energy:
Classical Treatment: E = 1/2mv2
Einstein: Mass-Energy Equivalence, E = mc2 (c = 3x108 m/s)
Mass is a form of energy and mass and energy are
interconvertible. Total mass + energy in any given process is
constant.
3. Charged Particles: Charges on particles have associated electric
and magnetic fields (wave-like properties).
4. Nomenclature:
Electron: e- = bPositron: e+ = b+
Proton: 1H+ = p+
Neutron: 1n = n
Deuteron: 2H+ = d+
Alpha: 4He2+ = a2+
Properties of Electromagnetic Radiation (EMR): EMR
is Often Called “Pure Energy” or “Light”.
1. Mass: EMR has no mass.
2. EMR is composed of oscillating electric & magnetic fields.
3. Charge: EMR has no charge.
4. Energy: EMR has energy.
classical kinetic energy.
However, it is not considered to be
5. EMR exhibits both wave-like and particle-like properties.
Wave Properties: EMR was first depicted in the form of a wave by
Maxwell in 1864.
Maxwell stated we can describe light, or EMR by the “wave
equation”, c = ln, where c = the speed of light, l = the wavelength,
and n = the frequency of the oscillation (n is proportional to 1/l and
l is proportional to 1/n. In other words, the shorter the wavelength,
the higher the frequency.
EMR Undergoes the Following Wave-like Properties.
1. Optical Interference:
2. Polarization:
3. Reflection:
4. Refraction:
5. Diffraction:
Wave Properties: All of this seemed to be a reasonable description
until 1901.
1901: Max Planck demonstrated that E was proportional to n, and
that EMR could possess particle-like properties…, i.e., a “photon”
or “quantum of light”.
Planck determined that E = hn, where h = Planck’s Constant.
Particle-like Properties of EMR Continued.
EMR can be completely characterized by the following two
mathematical equations.
c = ln
E = hn
We need only to know one of the three variables to calculate the
other two.
E = hn = hc/l
Important constants and values to consider:
h = 6.6x10-27 erg-s = 4.1x 10-15 eV-s
1 eV = 1.6x10-12 erg
1 J = 107 erg (SI unit is the joule)
c = 3x108 m/s = 3x1010 cm/s
Wavelength: 1 nm = 10-9m = 10-7cm
1 Angstrom (Å) = 0.1nm = 10-10m = 10-8cm
Concepts of Electromagnetic Radiation (EMR):
1. Units of Energy: We use the erg or the eV in this course; the
traditional unit in Radiation Sciences is the eV.
2. Definition: One electron-volt (eV) is the kinetic energy gained by
one electron when accelerated through a potential difference of
one volt (V).
Biological Effects of EMR with energy of 1ev versus 1MeV: Must
evaluate the chemical consequences of the action of EMR of
various energies (See the EMR spectrum on page 19 of handout).
1. For l ≥ 5-10cm up to miles in length: Radiowaves or microwaves
with E < 10-3-10-10 eV.
2. For l ≥ 700nm: Infrared with E = 0.01-1eV.
These type of radiations cause increases in the translational,
rotational, and vibrational motion of molecules. The resulting
increase in molecular energy is often converted to heat, as in a
microwave oven or infrared heating lamp.
3. For l = 300-700nm: Visible spectrum with E = 1-2 eV.
In the visible portion of the spectrum, a single photon of light can
now begin to initiate a chemical reaction by electronic excitation.
Electrons in molecules can be excited to higher energy levels,
where they become highly reactive.
However, this is the wavelength range to which we are continually
exposed. Only a few, select, beneficial reactions are initiated
above 380nm. For example… 11-cis-retinal is the reactive absorber
in rhodopsin, the retinal rod cell pigment which has an absorption
maximum of ~520 nm. Conversion to all trans-retinal form results
in dissociation of retinal and a conformational change in opsin,
which triggers a nerve impulse interpreted by the brain as sight.
Exercise: Calculate the energy of this photon (520 nm) in eV.
E = hn = hc/l = (4.1 x 10-15 ev-s)(3x108m/s)/(520 x 10-9m)
E = 2.4 eV
Another beneficial reaction initiated by visible excitation is the
absorption of 680nm light by chlorphyll. This induces electron
transport processes that result in photosynthesis.
4.
l = less than 200 to 380nm: UV light
300-380nm: near UV
200-300nm: UV
<200nm: vacuum UV
Between 250-310nm, 4-5eV, nucleic acids and proteins begin to
absorb light.
Excitation: We are still in the energy range (UV) where molecular
excitation occurs. Direct electronic excitation can damage nucleic
acids & proteins, leading to mutations and cell death.
Fortunately, ozone in the upper atmosphere acts as a protective
absorber, screening out virtually all light below 290 nm.
However, even UV with l = 290-350 nm has enough energy to
cause substantial damage to cells; UV-A & UV-B in this range can
cause sunburn and skin cancer.
It is not until we get to the vacuum UV or X-ray range that
ionization begins to occur.
Ionization Energy: The Ei of an atom or molecule is the amount of
energy required to remove (to infinity) an electron from the atom
or molecule isolated in free space and in its ground electronic
state.
Ionizing
Radiation:
Subatomic
electronic
particles
or
electromagnetic waves that are energetic enough to detach
electrons from atoms or molecules.
The ionization potential of most molecules is ~10eV.
Ion Pair: A positively charged ion and a negatively charged ion
produced by the addition of sufficient energy to a neutral atom or
molecule to cause it to dissociate into oppositely charged
fragments.
hn
Example: H2O
H2O*
H2O·+ + e- IP = 12.6 eV
hn
C6H6
C6H6*
C6H6·+ + e- IP = 9.25 eV
X-rays and Gamma (g)-rays:
1. X-rays: Originate from orbital electron transitions or orbital
electron rearrangement. Typically, X-rays between 10 and 11 keV
are studied very little as they have limited penetrating ability.
2.
g-rays: Originate from the unstable nucleus of an atom as it is
undergoing decay.
We usually deal with X-rays or g-rays with E 11 keV.
As stated above, X-rays and g-rays have different points of origin.
We can describe X-rays and g-rays using the two equations for
EMR.
Exercise: Calculate the energy of the characteristic X-ray of W.
KL transition of 0.2 Å = 2x10-9cm
E=hc/l = (4.1 x 10-15 eV-s)(3x1010cm/s)/2x10-9cm = 61500 eV (62keV)
THERFORE, SINCE THE IONIZATION POTENTIAL for MOST
MOLECULES is ~10eV, YOU CAN SEE WHY g- and X-rays are
TRULY IONIZING RADIATIONS!
THESE TYPES of RADIATIONS have SUFFICIENT ENERGY in ONE
PHOTON to IONIZE MANY MOLECULES.
Example: Co-60 has 2g photons (1.17 MeV and 1.33 MeV) of
average photon energy of 1.25 MeV. How many molecules can a
single g-photon of Co-60 ionize?
1.25x106 eV/10eV/molecule = 125,000 molecules!
However, the ionization process is not perfectly efficient. For
example, 34eV of energy is deposited for each ion pair formed.
If all of the energy were deposited, then:
1.25x106 eV/34eV/molecule = 37,000 molecules would be ionized.
Thus, photons of X- or g-radiations represent large individual
“packets” of energy. Each of these “packets” can ionize many
molecules and initiate chemical events that lead to biological
damage.
A radiation dose that is lethal to a human being deposits the same
amount of energy as the heat absorbed by drinking one sip of hot
coffee. The critical difference is not the total energy involved, but
the size of the energy “packets”.
Introductory Radiation Biology
Lecture 2: August 26, 2010.
Atomic Structure: The atom is composed of 3
subatomic particles
1. Proton (p+): mass = 1.007593 amu = 1.7 x 10-24g
2. Neutron (n): mass = 1.008982 amu = 1.7 x 10-24g
3. Electron (e-): mass = 0.000549 amu = 9.1 x 10-28g
mp+ = mn >> meTherefore, the atomic weights of all stable elements are known.
The electronic structure of the atom is described by the Bohr
model. Electrons orbit the nucleus in distinct shells. Electrons
can be excited into empty orbitals of higher energy. Transition
back to a lower energy state results in the release of EMR (i.e.,
fluorescence, phosphoresence, X-rays).
Nuclide: Any nucles plus its orbital electrons. Defined as follows:
A X
Z
Where A is equal to the atomic mass (protons + neutrons), Z is
equal to the atomic number (number of protons), and n = A-Z.
Isotope: Is an atom of the same element, having the same number
of protons, but differing numbers of neutrons.
11
6C,
12
6C,
13
6C,
14
6C
Isomers: Atoms that have a constant atomic mass (A) and atomic
number (Z), yet they contain a different energy arrangement of the
nucleons.
Example: 99m43Tc versus
99g Tc
43
Binding Energy of Nucleons: Nucleons (p+, n) are held together in
a very small volume of high positive charge density. Short-range
nuclear forces overcome charge repulstion between protons. We
can calculate the BE (binding energy) for nucleons).
Remember, energy and mass are interconvertible (E = mc2).
Dm = mtotal – mnucleus = BE
Some of the mass of the individual p+ & n is converted to binding
energy which holds the nucleus together. Therefore, the mass of
the nucleus is less than the total mass of p+ + n.
Example (Binding Energy per Nucleon: Consider the 42He atom.
Dm = mtotal – mnucleus = BE
Mass of Nucleus:
Measured atomic mass = 4.003873 amu
Mass of 2 electrons = 0.001098 amu
Mass of Nucleus = 4.002775 amu
Mass total:
2 x mp+ = 2 x 1.007593 = 2.015186 amu
2 x mn = 2 x 1.008982 = 2.017964 amu
Mass total = 4.033150 amu
Dm = mtotal – mnucleus = BE
Dm = 4.033150 – 4.002775
Dm = 0.030375 amu
Mass Energy: 1amu = 931 MeV
So, Binding Energy (BE) = 0.030375 amu (931MeV/amu) = 28.28 MeV
Binding Energy per Nucleon = 28.28 MeV/4 nucleons = 7.07
MeV/nucleon
Various models of nuclear structure exist. One thing is very certain;
there are quantized energy levels which nucleons occupy in the
nucleus. We can consider this similar in concept to the arrangement
of electrons in atomic orbitals.
Properties
of
Stable
Nuclei:
Systematic
investigations of nuclei indicate some general rules
regarding nuclear stability.
1. If there is more than one proton (p+) in the nucleus, then there
must be some neutrons.
2. There are no stable nuclides with Z > 83. 20983Bi is the heaviest
element with stability. This is the maximum number of nucleons (p
+ n) that can be packed in the nucleus and have stability.
3. Even numbers of nucleons (p or n) are preferred. Only 4 stable
odd-odd nuclides exist: 21H, 63Li, 105B, 147N.
4. Stable nuclides appear to cluster around a line of stability. For
example, for each Z, there appears to be only certain numbers of n
that will result in stability.
Line of Beta Stability:
Thus, very often, unstable nuclei are either proton rich or neutron
rich.
Also, odd-odd combinations can prompt instability
5. “Magic Numbers” which result in rather exceptional stability do
exist.
Either N or Z = 2, 8, 20, 28, 50, 82, 126
These are closed shells, analogous to those seen in electronic
structure 2n2 e-.
Modes of Radioactive Decay:
1. Alpha Decay: Fast moving monoenergetic helium nuclei. This
decay only occurs in elements of very high molecular weight.
Decrease of 4 in atomic mass (A) and 2 in atomic number (Z).
2. Negatron (b-): Negatively charged electrons released from the
nuclei of neutron rich radionuclides (n
p + b- + antineutrino).
Increase of +1 in atomic number.
3. Positron (b+): Positively charged electrons are released from the
nuclei of proton rich radionuclides. (p
n + b+ + neutrino). No
change in mass number, but decrease of 1 in atomic number.
4. Gamma Ray Decay: The nucleus rids itself of excess energy by
the emission of photons (all having the same discrete energy).
When gamma emission takes place between two states of
measurable lifetime, gamma decay is called isomeric transition. In
gamma decay, the number of nucleons does not change!
5. Electron Capture (EC): Occurs when a K orbital electron interacts
with the nucleus, combining with a proton to form a neutron and a
neutrino (e- + p n + neutrino). Loss of 1 proton gain of 1 neutron
per nucleus.
6. Internal Conversion: In most modes of decay where gamma rays
are normally emitted, the excited nucleus may interact with an
inner orbital electron, with all of the excitation energy being
transferred to that electron. The electron will be ejected from the
atom. Conversion electrons are monoenergetic.
Radioactive Decay: Spontaneous release of
energy in the form of subatomic particles or EMR
in an attempt to reach a more stable state.
1. Alpha Decay: Fast moving monoenergetic helium nuclei. This
decay only occurs in elements of very high molecular weight.
Decrease of 4 in atomic mass (A) and 2 in atomic number (Z).
An alpha particle is a 42He atom:
The radioactive decay mechanism is as follows:
A X
Z
A-4
Z-2Y
+ 42He + g + Q
Q value: The energy release by the decay process. It
is equal to the mass of the parent nucleus minus
the mass of the decay products. If it is a positive
number, decay can occur.
Example: Radium-226 decay.
226
88Ra,
t1/2 = 1620y
(a2 = 4.60MeV, 6.5%)
(a1 = 4.78MeV, 93.5%)
(g = 0.186MeV)
222
86Rn, t1/2
= 3.8d
Arrows go to the left. A decreases by 4 and Z decreases by 2.
Example of Q: Consider Pathway for a 1 (93.5%).
Q = Dm(931 MeV/amu) = (mp - (mD + ma)(931MeV/amu)
Mass of Parent = 226.0254 amu
Mass of Daughter = 222.0175 amu
Mass of Alpha = 4.0027 amu
Change in mass:
Dm = 226.0254 – (222.0175 + 4.0027)
Dm = 0.0052 amu
Mass Energy: 1amu = 931 MeV
Q = 0.0052 amu (931MeV/amu) = 4.87 MeV
Example of Q: Consider Pathway for a 2 (6.5%).
Q = Ea + Eg + Recoil E
Recoil E = (ma/mrecoil)Ea1 = (4/222)4.78MeV = 0.086MeV
Q = 4.60MeV + 0.186MeV + 0.086 MeV = 4.87MeV
Summary: Ra-226 decay.
Ra-226 loses a 42He atom during decay. Energy is also released in the
form of KE of the 42He atom.
The emission is monoenergetic, indicating the existence of discrete
energy levels in the nucleus.
Q cannot vary from parent to daughter. The total energy loss from
parent to daughter is ALWAYS the same!
a2 decay allows the nucleus to go to an intermediate energy level (i.e.,
0.186MeV above ground state). Then the nucleus eliminates the
remainder of the energy (sometime later, ~1ns) as EMR (g photon).
The gamma photon actually comes from the daughter nucleus
(Rn).
So, from this example, you can see that there is more than a
single pathway by which E is lost.
Sometimes, radioactive decay can leave the daughter nucleus
in an “excited state”. The release of E from this “excited state”
occurs via g-photon emission.
2. Negatron (b-): Negatively charged electrons released from the
nuclei of neutron rich radionuclides (n
p + b- + antineutrino).
Increase of +1 in atomic number.
A negatron is a 0-1e- (b-):
The radioactive decay mechanism is as follows:
A X
Z
A
Z+1Y
+ 0-1e + n + g + Q
Example: Phosphorus-32 decay.
32
15P, t1/2
= 14d
(b = 1.72MeV, 100%)
32
16S,
stable
Arrow goes to the right. Note a net increase in Z of 1
(neutron to a proton.
Q = 1.72 MeV
Example of Q: Consider Pathway for b 1 (100%).
Q = Dm(931 MeV/amu) = (mp - (mD)(931MeV/amu)
Mass of Parent = 31.98412 amu
Mass of Daughter = 31.98227amu
Mass of Electron = Already accounted for because Z increases by 1
Change in mass:
Dm = 31.98412 – (31.98227)
Dm = 0.00185 amu
Mass Energy: 1amu = 931 MeV
Q = 0.00185 amu (931MeV/amu) = 1.72 MeV
With an energy of 1.72 MeV, we would expect the b- to be
monoenergetic. However, this is not the case. Rather, a
continuum of b- energy is observed up to the maximum:
Se the graph below.
Typically, Eb-(average) ~ 1/3 Emax.
To avoid the necessity of abandoning conservation laws (E
& spin), we postulate another particle, the antineutrino (n),
which has zero charge, zero mass, and a spin of 1/2. The
antineutrino carries away the excess decay energy not
imparted to the b-.
Q = Eb- + En + Erecoil
Summary of Beta Decay: Results in transforming a neutron
to a proton in the nucleus. An antineutrino is emitted in
conjugation with the b- particle. Even though the Etotal for
the decay is always the same, Eb- is a contnuum with Eb(average) ~ 1/3 Emax.
Beta decay occurs in neutron rich radionuclides.
Gamma emission can accompany b- decay.
60
27Co, t1/2
= 5y
(b = 0.32MeV, 100%)
g1 = 1.17MeV
g1 = 1.33MeV
60
28Ni,
stable