Radiobiology

Course Leader:
Dr. Mohammad Abuqbeitah
Msc. PhD. NM & MP

Dr. Abuqbeitah 1
Objectives
• History of Radiation Biology
• Basic Concepts of Radiation Biology
• Molecular Radiation Biology
• Mechanistic, Modeling, and Dosimetric Radiation Biology
• Clinical Radiobiology for Radiation Oncology
• Individual Radiation Sensitivity and Biomarkers: Molecular
Radiation Biology
• Radiobiology of Accidental, Public, and Occupational Exposure
• Radioprotectors, Radiomitigators, and Radiosensitizers
• RBE
• Direct and Indirect Radiation Effects
• Radicals production
• Oxygen effect
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Overview
Radiation biology: is the study of the effects of ionizing radiation on biological tissues and living organisms.

Multidisciplinary radiobiological research forms the scientific basis of various disciplines such as radiation protection,
radiotherapy, and nuclear medicine.

The goal of radiobiological research is to understand better the effects of radiation exposure at the cellular and
molecular levels in order to determine the effects on health.

Radiobiology encompasses various disciplines including biology, clinical applications, pharmacy, environmental and
space life sciences, which make radiobiology overall a broad and rather complex topic.

One of the most significant contributions of radiobiological research was the discovery of the oxygen effect, which
emphasized free radical production mechanisms in the radiation action on biological and chemical systems.

Experiments on cellular colony formation showed that, in the presence of oxygen, more cell death occurred for the
same irradiation dose.

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 • the International Commission on Radiation
Protection (ICRP) was formed in 1928 to provide • [Link]
history recommendations and guidance about protecting
humans against the risks of ionizing radiation.
[Link]/

• The United Nations Scientific Committee on Effects

of Atomic radiation (UNSCEAR) was then formed in • [Link]
1955 to determine the level and effects of ionizing [Link].o
radiation from atomic bombs and nuclear accident rg/
exposures.
• 1955, the US Academy of Sciences Committee on
Biological Effects of Ionizing Radiation (BEIR) was
established to determine and guide risks of radiation • [Link]
exposure on living organisms. [Link]/
• 1957 , The International Atomic Energy Agency
(IAEA), was created to guide and advise on safe
radiation dose regulations for workers and the public

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 • Wilhelm Conrad Röntgen (1845–1923)
experimented with Crookes tubes and in
November 1895 detected electromagnetic
radiation of a subnanometer wavelength range
(X-rays).
• He earned the fist Nobel Prize in Physics in
1901.

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• Henri Becquerel (1852–1908) discovered radioactivity in 1896 while
studying phosphorescent uranium salts.
• In the same year, upon experimenting with non-phosphorescent
uranium salts, he concluded that the penetrating radiation came
from the uranium itself.
• He was awarded the Nobel Prize in Physics in 1903

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Ernest Rutherford

• Ernest Rutherford (1871–1937) is known as

the father of nuclear physics.
• He was the first to suggest the existence of
nuclei.
• He developed the idea that radioactivity
involved spontaneous disintegration of
atoms.
• In 1908, he was awarded the Nobel Prize in
Chemistry “for his investigations into the
disintegration of the elements, and the
chemistry of radioactive substances.”

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Pierre and Marie Curie
• Pierre Curie (1859–1906) and his wife Marie
Salomea Skłodowska-Curie (1867–1934)
discovered the elements radium and polonium.
• The term “radioactivity” was coined by Marie
Curie.
• Pierre Curie discovered nuclear energy by
identifying the continuous emission of heat from
radium particles.
• In 1903, Pierre and Marie Curie were awarded
the Nobel Prize in Physics (together with
H. Becquerel) for the discovery of radioactivity.
• In 1913, H. G. Wells coined the term “atomic
bomb” mentioned in his novel “The World Set
Free

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Cartoon from “Life,” February 1896. The New
Roentgen Photography. “Look pleasant, please”

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Physics and chemistry of radiation
interactions with matter
• Radiations are broadly categorized into
natural and man-made sources .
• Both natural background radiation from
cosmic and terrestrial sources, and man-
made radiations, cause ionization of
atoms or molecules, which may cause
injury to cells.
• More than 90 % of radiation exposure to
man occurs from natural sources e.g.
cosmic rays, and terrestrial sources that
comes from radionuclides in the earth’s
crust, air, food and water and the human
body itself.
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• Ionizing radiation: is the process of • Non-ionizing radiations: are generally
removing one or more electrons from considered harmless to biological
atoms by the incident radiation tissues at levels below those that
• The ionized or excited atom or molecule cause heating effects
may either fragment producing free radicals
• Cellular phones, radar, infrared,
or return to the parent state.
radiowaves, microwaves, visible light,
• If the energy transferred by ionizing ultrasound fall into this category.
radiation to the atom is insufficient to eject
orbital electrons, the electrons may be • However, some molecules can be
raised from lower to higher orbitals and the ionized with very little energy, and far
atom is said to be excited. UV radiation can behave similarly to X
and γ rays.

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Types of ionizing radiation
Particle radiation are directly ionizing:
• individual particles with adequate kinetic energy can
directly disrupt the atomic structure of the
absorbing medium through which they pass
producing chemical and biological damage to
molecules.
Electromagnetic radiations are indirectly ionizing:
• because they do not produce chemical and
biological damage themselves but produce
secondary electrons (charged particles) after energy
absorption in the material.

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How Radiation Kills Living Cells/Tissues
• The discovery of DNA structure, as a double-
stranded helix with nucleotides as the basic units by
Watson and Crick in the 1950s.
• Radiological studies showed that radiation can kill
exposed cells by damaging the DNA in the nucleus,
which if not repaired prove fatal for cells.
• Since tumour cells divide faster than normal cells, it
was hypothesized that radiation could kill these
cells more efficiently.
• Due to hypoxia in the tumour core, tumour cells
showed resistance to radiation, leading to
disappointment amongst radiation therapists.
• Research was undertaken to develop sensitizers of
tumour cells to radiation
• oxygen being the best radiosensitizer.
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• Today, more than 40% of cancer patients are treated by radiation for therapeutic and
palliative procedures.
• The technology consists of carefully targeting radiation beams and certain
radiopharmaceuticals to destroy cancer cells while minimizing the damage to
nearby healthy cells.
• Radiobiological studies in the 1920s helped design patient treatment protocols in
what is popularly called fractionated radiotherapy.

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 Limitations in
Radiotherapy
• Radiation therapy of cancer patients is limited by any toxicity towards normal cells.
• The next goal of radiobiology was to inflict selective damage on a tumour whilst
sparing normal cells.
• Based on radiobiological effectiveness of different cell types to the same dose of
radiation, particle radiation therapy and ion beam therapies were being developed to
improve the radiotherapy for patients.
• Today, the public’s major radiation exposures arise from medical applications such as
diagnostic X-rays and CT scans to diagnose diseases, and cancer radiotherapy,
including treatment of injuries.
• Therapeutic drugs with radioactive material attached, known as
radiopharmaceuticals, are also routinely used in clinics to diagnose and treat some
diseases. T
• hese procedures are a valuable tool to help doctors save lives through quick and
accurate diagnosis

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Therapeutic window

Therapeutic window

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LNT (Linear No Threshold Model)

The LNT model implies that all exposure to ionizing

radiation is harmful, regardless of how low the dose
is, and that the effect is cumulative over lifetime.

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‫‪:‬اﻟﻨﺺ ﻻ ﯾﻌﻜﺲ اﻟﻘﺎﻋﺪة اﻟﻌﺎﻣﺔ‪ ،‬ﻟﻜﻨﮫ ﯾﺸﯿﺮ إﻟﻰ أن‬

‫‪1‬‬ ‫اﻟﺠﺮﻋﺎت اﻟﻌﺎﻟﯿﺔ ﻗﺪ ﺗﻜﻮن ﻣﺮﺗﺒﻄﺔ ﺑﺤﺪوث اﻟﺴﺮطﺎن‪ ،‬ﻟﻜﻨﮫ ﻻ ﯾﻘﻮل إﻧﮭﺎ اﻟﺴﺒﺐ اﻟﻮﺣﯿﺪ‪ ،‬ﺑﻞ ﯾﺆﻛﺪ أن اﻟﺠﺮﻋﺎت‬
‫‪.‬اﻟﻤﻨﺨﻔﻀﺔ وﺣﺪھﺎ ﻗﺪ ﻻ ﺗﻜﻮن ﻛﺎﻓﯿﺔ ﻹﺣﺪاث اﻟﺴﺮطﺎن ﺑﺪون ﻋﻮاﻣﻞ إﺿﺎﻓﯿﺔ‬

‫‪2‬‬ ‫اﻟﻌﻮاﻣﻞ اﻟﺠﯿﻨﯿﺔ واﻟﺒﯿﺌﯿﺔ ﻗﺪ ﺗﻠﻌﺐ دوًرا ﺑﺠﺎﻧﺐ اﻟﺠﺮﻋﺎت اﻟﻤﻨﺨﻔﻀﺔ ﻣﻦ اﻹﺷﻌﺎع ﻓﻲ اﻟﺘﺴﺒﺐ ﺑﺎﻟﺴﺮطﺎن‪ ،‬ﻟﺬا ﻻ‬
‫‪.‬ﯾﺠﺐ دراﺳﺔ اﻟﺠﺮﻋﺎت اﻟﻤﻨﺨﻔﻀﺔ ﺑﻤﻌﺰل ﻋﻦ اﻟﻌﻮاﻣﻞ اﻷﺧﺮى‬

‫‪:‬اﻟﺨﻼﺻﺔ‬
‫‪Dr. Abuqbeitah‬‬ ‫‪23‬‬
‫ﻀﺎ أو ﻣﺮﺗﻔًﻌﺎ‪ ،‬ﻗﺪ ﯾﻜﻮن ﺟﺰًءا ﻣﻦ ﻋﻤﻠﯿﺔ‬
‫اﻟﻨﺺ ﻻ ﯾﻨﺎﻗﺾ اﻟﻘﺎﻋﺪة اﻟﻌﺎﻣﺔ‪ ،‬ﻟﻜﻨﮫ ﯾﺆﻛﺪ أن اﻟﺘﻌﺮض ﻟﻺﺷﻌﺎع‪ ،‬ﺳﻮاء ﻣﻨﺨﻔ ً‬
‫ﻣﻌﻘﺪة ﺗﺸﻤﻞ ﻋﻮاﻣﻞ أﺧﺮى ﻓﻲ ﺗﻜﻮﯾﻦ اﻟﺴﺮطﺎﻧﺎت‬
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A sequence of energy
deposits

• The energy of an original 1.25

MeV photon is deposited in
five subsequent Compton
processes
• The electron mean range is
much shorter starting at
about 2 mm going down to
about 36 μm in the last
Compton scattering (which
is still larger than a typical
cell diameter)

‫ﻣﺒﺪأ اﻷﺳﺎﺳﻲ ھﻮ أن ﻓﻮﺗﻮﻧًﺎ‬

‫ﻋﺎﻟﻲ اﻟﻄﺎﻗﺔ ﯾﻔﻘﺪ طﺎﻗﺘﮫ ﺗﺪرﯾﺠﯿًﺎ‬ Dr. Abuqbeitah 27
‫ﻣﻦ ﺧﻼل ﺳﻠﺴﻠﺔ ﻣﻦ ﺗﻔﺎﻋﻼت‬
‫ ﻓﻲ ﻛﻞ‬.‫ﻛﻮﻣﺒﺘﻮن اﻟﻤﺘﺘﺎﻟﯿﺔ‬
‫ ﯾﺘﻢ ﻧﻘﻞ ﺟﺰء ﻣﻦ طﺎﻗﺔ‬،‫ﺗﻔﺎﻋﻞ‬
Dependence of absorption on atomic number
• The radiation energy deposition depends on • Bone is mainly comprised of calcium whereas
the : soft tissues are comprised of low atomic number
elements such as carbon, hydrogen and oxygen.
1. Energy of the radiation
2. Atomic number (Z) of the absorbing • The mass absorption coefficient for the Compton
material. process is nearly independent of atomic number.
• Compton and photoelectric effects are vital for
appropriate applications in X- ray diagnosis and
cancer therapy.
• In radiotherapy, high-energy photons in the range
of 1-10 MeV are preferred because absorbed
dose is nearly the same in bone and soft issues
Problem: WHY The probability that a photon • low energy photons are preferred in diagnosis
will be absorbed in bone is about six times that because of the much desired large contrast in
in an equal thickness of soft tissues.? absorption of these tissues.

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Quantification in radiobiology
• For quantification in radiobiology, the detailed description of the stopping power is not used
• Conventionally, the linear energy transfer LET is used instead and only takes electronic
interactions into account
• The difference between LET and electronic stopping lies in their origin
• The electronic stopping is focused on the energy loss of the impacting particle, and it has a
negative sign as it acts as a friction force.
• The LET has a positive sign, and it is the energy that the target sees deposited in itself; this
“positive amount of energy” creates the nonequilibrium dynamics, which are the first radiation-
induced effects.
• The LET and the electronic stopping are equal for big samples, which is the case in radiobiology.

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Linear Energy Transfer
• For a particular absorber, the rate of loss of energy depends on the :
1. Energy
2. type of radiation
3. the density of the material .
• LET is defined as the average energy deposited per unit length of track of radiation and the unit is keV/
μm.
• LET varies along the length of the track of charged particles because the charged particle slow down
with depositing energy in tissue .
• The rate of energy transferring increases as particles slow down
• There is a peak of energy deposition at the end of the track (the Bragg peak).
• LET essentially indicates the quality of different types of radiation and is important because the
biological effect of a radiation (its relative biological effectiveness, RBE) depends on its average LET.
• Radiations are categorized into low and high LET radiations with particulate radiations usually being
high LET radiations whereas X and γ rays are low LET radiations due to their sparse ionizations (.
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 • The RBE of a radiation increases with its LET up to a
value of about 100 keV/μm
• Above this value cause the biological effect (overkill).
• Energy loss events are randomly distributed along the
track of the photon or charged particle.
• For low LET radiations the energy deposition events
along the track of the photon are sparse relative to the
dimensions of biomolecules such as DNA.
• The result that photons may pass through such a
molecule without depositing any energy.
• For such radiations the amount of energy deposited in
a region of the track similar in dimensions to biological
molecules also various widely from a few eV up to
100s of eV.
• For high LET radiation the energy loss events are much
more closely spaced and significant energy will be
deposited along all parts of the track similar in
dimension to biomolecules

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• Equivalent dose is expressed as a summation to include the effects of irradiation of tissue by more
than one type of radiation.
• In the past the unit rem (radiation equivalent man) was used to compare doses received by different
types of radiations (100 rem = 1 Sv).
• The quality factor for low LET radiations is 1 so that for low LET radiations 1 Sv = 1 Gy. H T = ∑WR x DT

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 Effective dose Effective

• Dose is used to estimate the risk of radiation in humans.

• It is sum of the products of equivalent doses to each
organ/tissue (HT) and the tissue weighting factor (WT) .
• E = ∑ W T x HT The unit of effective dose is the Sievert (Sv).
• Collective dose is defined as the dose received per person in
Sv multiplied by the number of persons exposed per year
• Man-sievert per year as a unit is generally used for protection
purposes and in population response calculations.

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