RADIATION BIOPHYSICS

Dr. Sreejaya. R NSS HINDU COLLEGE CHANGANACHERRY

 Atoms, which have the same atomic number but different mass numbers are called isotopes. A stable isotope is one in which the nucleus has equal number of protons and neutrons. If the proton-neutron ratio of atoms is more than one, they become unstable and are called radioisotopes, The process of emission of electromagnetic radiation by the radioactive isotopes is called radioactivity, Radioactivity may be natural or artificial manmade.

The radio activity classified into 1. Natural radioactivity: The spontaneous emission of highly penetrating radiations such as , and rays by the heavy elements like uranium, radium, thorium, etc.
2. Artificial radioactivity: The process by which- the light elements are made into radioactive substances is called artificial radioactivity They emit electrons, neutrons, positrons and rays The important artificial radioisotopes include tritium (H3), sodium (Na24), phosphorous (P32), cobalt (CO60), carbon (C14), iodine (I), sulphur (S35), etc.

 Properties of Radioactive Radiation (Ionising Radiations) (A) Alpha Particles ( rays)

These are positively charged particle. It is identified as nuclei of helium atom with two (2) protons and two (2) neutrons. They move with high velocities ranging from 1.4 x 109 to 1.7 x 10 9 cm per second. They have greatest ionizing power than particle. They have shortest penetrating power. The affect a photographic plate. They get scattered while passing through thin metal foil. They are deflected by electric and magnetic field. They are doubly charged helium, so they are called Helions.

(B)Beta Particles ( Rays) They are identified as electrons. They are negatively charged particle. It can penetrate through large thickness of matter. They are deflected by electric and magnetic field. They affect photographic plate. They move with high velocity (2.36 x 108 - 2.83 x 108 cm/sec) They produce fluorescence and phosphorescence. They are readily scattered when passing through the matter. They carry one unit negative charge. They produce ionization in air but the number of ions produced is hardly1/100 th those produced by rays.

(c) Gamma Rays (:) These are electromagnetic waves of short wavelength. They have the same velocity as that of light (3 x 1010 cm/sec). They do not contain any charge particle. They are not deflected by electric or magnetic field. They ionize the gas through which it pass although the ionization power is very low. They produce fluorescence. Their penetrating power is very high. They affect photographic plate.

INTERACTION OF RADIATION WITH MATTER There are three processes by which high energy radiation interacts with matter

1. photoelectric, 2. Compton and 3. electron-positron pair production processes.

1. The Photoelectric Effect. At lower energies (< 30 KeV) the photoelectric effect comes into operation. In this process all the energy of the incident radiation is utilized in ejecting a bound electron resulting in ionisation. Photoelectrons are absorbed locally, causing ionization and excitation. The photoelectric effect is predominant at low energies (<0.1 MeV) and for elements of high atomic numbers

2. The Compton Effect. At medium energies (< 10 MeV) the Compton effect is dominant. The Compton effect is inelastic scattering, wherein a photon transfers part of its energy to weakly-bound electrons (recoil electrons) and the scattered photon has reduced energy. The energy of the recoil electrons, absorbed locally will be the cause for further ionisation and excitation processes. The Compton effect is prominent at moderately high energies and for materials of low atomic number, and therefore of relevance in effects on biological tissues.

3. Pair Production. Radiations (Photons) with energies > 1 .02 MeV passing close to a nucleus of an atom can create, an electron-position pair (e-e+). Pair formation is greater in heavy elements than in lighter elements.

Units of Radioactivity: The units of radioactivity of an element is the measure of the rate at which it changes to the daughter element. It has been derived on the scale of Curie (Ci) The quantity of any radioactive substance disintegration of radioactive substance per second. Curie (Ci) The quantity of any radioactive substance which undergoes 3.7 x 1010 disintegrations per second. Millicurie (mCi) Represents 3.7 x 107 radioactive disintegrations per second.

Microcurie Represents 3.7 x 104 radioactive disintegrations per second.

Becquerel (Bq). It is the quantity of radioactive material in which one nuclear disintegration occurs in one second. 1 Bq = 2.7x1011Ci. Rutherford (rd): One rutherford is the amount of radioactive substance which undergoes 106 disintegration per second.

 DOSIMETRY Radiation dosimetry is the measurement and calculation of the absorbed dose in matter and tissue resulting from the exposure to indirect and direct ionizing radiation Dose is reported in gray (Gy) for matter or sieverts (Sv) for biological tissue 1 Gy or 1 Sv = 1 joule per kilogram. Dose is often reported in rads and dose equivalent in rems. 1 Gy = 100 rad 1 Sv = 100 rem.

 Radiation dose refers to the amount of energy deposited in matter and/or biological effects of radiation, and should not be confused with the unit of radioactive activity (Becquerel, Bq). several ways of measuring doses from ionizing radiation 1. Thermoluminescent dosimetry (TLD) or 2. Optically stimulated luminescence (OSL) 3. Medical dosimetry is the calculation of absorbed dose and optimization of dose delivery in radiation therapy.

 DETECTION AND MEASUREMENT OF RADIATION

A. GEIGER-MULLER COUNTER (GM TUBE) B. FOUNTAIN-PEN DOSIMETER C. PROPORTIONAL COUNTER D. SCINTILLATION COUNTER E. LIQUID SCINTILLATION COUNTER F. CRYSTAL COUNTER G.AUTORADIOGRAPHY

 AUTORADIOGRAPHY
Autoradiography is an important technique by which the routes and conversion of molecules in biochemical reactions occurring in cells are traced. The radioactive isotopes are stable only for definite periods and then they decompose to form other atoms or fragments of atoms. During this radioactive decay, many atoms produce radioactive emissions, which may be measured by special devices

 In this technique, the sample containing radioactive substance (a chromatogram or a tissue slice or a section of a plant or animal) is kept in close contact with a photographic plate or an X-ray film.
That is, the cells or tissues already exposed to radioactive isotopes are made to contact with a photographic emulsion for specific period . The emanating radiations affect the emulsion in the same way like that of light.

On development, the areas, which have been in contact with radioactivity could appear as spots on the film, thus producing the image of the specimen

 RADIOACTIVE TRACERS
Radioactive tracing was developed by George de Hevesy, who won the 1943 Nobel Prize for Chemistry for his pioneering work using radioactive tracers to study metabolic processes in plants and animals

A radioactive tracer, also called a radioactive label, is a substance containing a radioisotope that is used to measure the speed of chemical processes and to track the movement of a substance through a natural system such as a cell or tissue.
A number of different radioactive forms of hydrogen, carbon, phosphorus, sulfur, and iodine are commonly used in applications including biochemical assays, metabolism studies, and medical diagnostics.

 A radioactive tracer is identical in chemical composition to the compound of interest and is administered in minute amounts that do not perturb the experimental system.
The tracer behaves in exactly the same way as an unlabeled molecule, but the tracer molecule continually gives off radiations. The radiations can be detected with a Geiger counter, scintillation counter or other type of radiation detection instrument.

Applications of Radioactive tracers A Metabolic Research In metabolism research, radioactive tracers are frequently used in glucose clamps to measure rates of glucose uptake, fatty acid synthesis, and other metabolic processes. Tritium and carbon-14-labeled water and glucose are commonly used tracers for metabolic clamp studies. While radioactive tracers are sometimes still used in human studies, stable isotope tracers such as carbon-13 are more commonly used

Radioactive tracers are also used to study lipoprotein metabolism in humans and experimental animals

B. Medical applications Diagnostics In medicine, tracers are applied in a number of tests, such as technetium-99 in autoradiography Nuclear medicine, including single photon emission computed tomography (SPECT), positron emission tomography (PET) and scintigraphy. The urea breath test for helicobacter pylori commonly used a dose of carbon-14 labeled urea to detect h. pylori infection. If the labeled urea was metabolized by h. pylori in the stomach, the patient's breath would contain labeled carbon dioxide. In recent years, the use of the stable isotope carbon-13 has become the preferred method to minimize patient exposure to radiation

 Tritium (3H) frequently used as a tracer in biochemical studies. Carbon-11 is frequently used as a tracer in positron emission tomography, an imaging technique that allows for three-dimensional imaging of functional processes in the human body. Carbon-14 has been used as a tracer in both medical and scientific tests. Carbon-14 is frequently used to trace carbons through metabolic pathways. Phosphorus-32 is frequently used to label amino acids and phosphoproteins and is commonly used to study protein phosphorylation by kinases in biochemistry. Iodine-123 is used in nuclear medicine imaging, specifically to study thyroid function. Iodine-125 is frequently used in radioimmunoassays

Radio Iminuno Assay (RIA). One of the important applicaitons of radioactive tracers in biology and medicine is the Radio Immuno Assay (RIA) method. This method can he employed to assay substances present in small quantities (10-9 gm/ml) with a high degree of specificity. It can he used in the in vitro diagnostic monitoring of abnormalities of body functions, enzyme catalysts and other biochemical reactions The general principle of RIA is the quantitative measurement of the ratio of labelled antigen (Ag ) molecules to an unknown quanity of assay antigen (Ag) competing for the binding sites of a known quantity of an antibody (Ab).

 Radiation protection Radiation protection, sometimes known as radiological protection, is the science of protecting people and the environment from the harmful effects of ionizing radiation, which includes both particle radiation and high energy electromagnetic radiation Radiation protection can be divided into 1. occupational radiation protection, 2. medical radiation protection, 3. public radiation protection,

 There are three factors that control the amount, or dose, of radiation received from a source. Radiation exposure can be managed by a combination of these factors:
Time: Reducing the time of an exposure reduces the effective dose proportionally. Distance: Increasing distance reduces dose Distance can be as simple as handling a source with forceps rather than fingers Shielding: The term 'biological shield' refers to a mass of absorbing material placed around a reactor, or other radioactive source, to reduce the radiation to a level safe for humans

ICRP - International Commission on Radiological Protection):

Justification: No unnecessary use of radiation is permitted, which means that the advantages must outweigh the disadvantages. Limitation: Each individual must be protected against risks that are far too large through individual radiation dose limits. Optimization: Radiation doses should all be kept as low as reasonably achievable.

 Different types of ionizing radiation behave in different ways, so different shielding techniques are used.
Alpha particles (helium nuclei) are the least penetrating can be stopped by a single sheet of paper. Beta particles (electrons) are more penetrating, but still can be absorbed by a few millimeters of aluminum. shielding must be accomplished with low density materials, e.g. plastic, wood, water or acrylic glass Ultraviolet (UV) radiation is ionizing but it is not penetrating, so it can be shielded by thin opaque layers such as sunscreen, clothing, and protective eyewear. X-ray and gamma radiation are best absorbed by atoms with heavy nuclei; the heavier the nucleus, the better the

absorption.

 Nuclear medicine
In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals These radiopharmaceuticals, once administered to the patient, can localize to specific organs or cellular receptors Nuclear medicine is an ideal specialty to adapt to the new discipline of molecular medicine, because of its emphasis on function and its utilization of imaging agents that are specific for a particular disease process

 2D: Scintigraphy is the use of internal radionuclides to create two-dimensional

3D: SPECT is a 3D tomographic technique that uses gamma camera data from many projections and can be reconstructed in different planes. Positron emission tomography (PET) uses coincidence detection to image functional processes nuclear medicine studies that allow imaging of the whole body based on certain cellular receptors or functions. Examples are whole body PET scan or PET/CT scans, gallium scans, indium white blood cell scans, MIBG and octreotide scans The radionuclide introduced into the body is often chemically bound to a complex that acts characteristically within the body; this is commonly known as a tracer.

 Radiation therapy Radiation therapy (in American English), radiation oncology, or radiotherapy (in the UK, Canada and Australia), sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.
Radiation therapy is commonly applied to the cancerous tumor because of its ability to control cell growth. Ionizing radiation works by damaging the DNA of exposed tissue

cancerous cells may be more susceptible to death by this process as many have turned off their DNA repair ability during the process of becoming cancerous.

 Radiation may be prescribed by a radiation oncologist with intent to cure. It may also be used as palliative treatment (where cure is not possible and the aim is for local disease control or symptomatic relief) or as therapeutic treatment (where the therapy has survival benefit and it can be curative). It is also common to combine radiation therapy with surgery,

Most common cancer types can be treated with radiation therapy in some way. Radiation therapy works by damaging the DNA of cancerous cells. This DNA damage is caused by one of two types of energy, photon or charged particle. This damage is either direct or indirect ionization of the atoms which make up the DNA chain

 The amount of radiation used in photon radiation therapy is measured in gray (Gy), and varies depending on the type and stage of cancer being treated. For curative cases, the typical dose for a solid epithelial tumor ranges from 60 to 80 Gy, while lymphomas are treated with 20 to 40 Gy. Different cancers respond differently to radiation therapy. Before treatment, a CT scan is often performed to identify the tumor and surrounding normal structures. The patient is then sent for a simulation so that molds can be created to be used during treatment. The patient receives small skin marks to guide the placement of treatment fields

Types of radiation therapy 1. Brachy therapy uses sealed radioactive sources placed precisely in the area under treatment, and systemic radioisotopes are given by infusion or oral ingestion 2. Particle therapy is a special case of external beam radiation therapy where the particles are protons or heavier ions. 3. Intraoperative radiation therapy or IORT is a special type of radiation therapy that is delivered immediately after surgical removal of the cancer. This method has been employed in breast cancer (Targeted Intra operative radiation therapy or TARGIT), brain tumors and rectal cancers.

 SIDE EFFECTS OF RATION THERAPY Acute side effects Damage to the epithelial surfaces Mouth and throat sores Intestinal discomfort Infertility Swelling (edema or oedema) Late side effects Many late effects are reduced by fractionating treatment into smaller parts. Fibrosis Epilation (hair loss) Dryness Radiation proctitis Cancer Heart disease Cognitive decline Lymphedema

 Effects on reproduction During the first two weeks after fertilization, radiation therapy is lethal. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukemia and other tumours in the offspring.
In males previously having undergone radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy

 Biological Effects of Radiation

Whether the source of radiation is natural or manmadewhether it is a small dose of radiation or a large dose, there will be some biological effects

Radiation Causes Ionizations of: ATOMS

which may affect

MOLECULES
which may affect

CELLS
which may affect

TISSUES
which may affect

ORGANS
which may affect

THE WHOLE BODY

 Biological effects of radiation result primarily from radiation-induced chemical/biochemical changes. Radiation can cause genetic mutation and cell damage. Charged particles such as -rays and electrons damage living cells directly, whereas X-rays and -rays and neutrons damage indirectly X-rays and -rays have energies in excess of the ionisation threshold and, therefore, the ejected electrons are highly energetic and they in turn produce further ionisation due to secondary electrons ( rays) in neighbouring atoms., That is, ionisation is due to primary as well as secondary electron interaction processes with matter.

 1. Direct Effect If radiation interacts with the atoms of the DNA molecule, or some other cellular component critical to the survival of the cell, it is referred to as a direct effect. Such an interaction may affect the ability of the cell to reproduce and, thus, survive. If enough atoms are affected such that the chromosomes do not replicate properly, or if there is significant alteration in the information carried by the DNA molecule, Then the cell may be destroyed by direct interference with its life-sustaining system

 2. Indirect Effect: Radiolytic Decomposition of Water in a Cell

each cell, just as is the case for the human body, is mostly water. Therefore, there is a much higher probability of radiation interacting with the water that makes up most of the cells volume. When radiation interacts with water, it may break the bonds that hold the water molecule together, producing fragments such as hydrogen (H) and hydroxyls (OH). These fragments may recombine or may interact with other fragments or ions to form compounds, such as water, which would not harm the cell. However, they could combine to form toxic substances, such as hydrogen peroxide (H2O2), which can contribute to the destruction of the cell.

Cellular Sensitivity to Radiation

(from most sensitive to least sensitive)

Lymphocytes and Blood Forming Cells Reproductive and Gastrointestinal (GI) Cells Nerve and Muscle Cells
Lymphocytes (white blood cells) and cells which produce blood are constantly regenerating, and are, therefore, the most sensitive. Reproductive and gastrointestinal cells are not regenerating as quickly and are less sensitive. The nerve and muscle cells are the slowest to regenerate and are the least sensitive cells.

 Organ Sensitivity
(from most sensitive to least sensitive)

Blood Forming Organs Reproductive and Gastrointestinal Tract Organs Skin Muscle and Brain The blood forming cells were one of the most sensitive cells due to their rapid regeneration rate, the blood forming organs are one of the most sensitiveorgans to radiation. Muscle and nerve cells insensitive to radiation,. were relatively

 Whole Body Sensitivity Factors

Total Dose Type of Cell Type of Radiation Age of Individual Stage of Cell Division Part of Body Exposed General State of Health Tissue Volume Exposed Time Interval over which Dose is Received

 Radiation Effects
High Doses (Acute) Low Doses (Chronic)
High doses tend to kill cells, while low doses tend to damage or change them. High doses can kill so many cells that tissues and organs are damaged. This in turn may cause a rapid whole body response often called the Acute Radiation Syndrome (ARS).
Low doses spread out over long periods of time dont cause an immediate problem to any body organ. The effects of low doses of radiation occur at the level of the cell, and the results may not be observed for many years.

High Dose Effects

Dose (Rad)
15 - 25 50 100 150 320 - 360 480 - 540 1,100

Effect Observed
Blood count changes in a group of people Blood count changes in an individual Vomiting (threshold) Death (threshold) LD 50/60 with minimal care LD 50/60 with supportive medical care LD 50/60 with intensive medical care (bone marrow transplant)

 Other High Dose Effects a. Skin Burns b. Hair Loss c. Sterility d. Cataracts
Acute Radiation Syndrome (ARS)
Syndrome Organs Affected Sensitivity

Hematopoietic Gastrointestinal Central Nervous System

Blood forming organs Gastrointestinal system Brain and muscles

Most sensitive Very sensitive Least sensitive

 Categories of Effects of Exposure to Low Doses of Radiation

Genetic Somatic In-Utero

Genetic Effects: Mutation of the reproductive cells passed on to the offspring of the exposed individual Somatic Effects: Effect is suffered by the individual exposed Primary consequence is cancer In-Utero Effects: Effects of radiation on embryo/fetus

Genetic Effects The Genetic Effect involves the mutation of very specific cells, namely the sperm or egg cells Somatic Effects Effect is suffered by the individual exposed Primary consequence is cancer Lung cancer - uranium miners Bone cancer - radium dial painters Thyroid cancer - therapy patients Breast cancer - therapy patients Skin cancer - radiologists Leukemia - bomb survivors, in-utero exposures, radiologists, therapy patients In-Utero Effects Effects of radiation on embryo/fetus Intrauterine Death Growth Retardation Developmental Abnormalities Childhood Cancers

 9. Radiation Risk: With any exposure to radiation, there is some risk The approximate risks for the three principal effects of exposure to low levels of radiation are:
Effect Excess Cases per 10,000 exposed per rad

Genetic Somatic (cancer) In-Utero (cancer) In-Utero (all effects)

2 to 4 4 to 20 4 to 12 20 to 200

REFERENCES
1. Reactor Concepts Manual Biological Effects of Radiation USNRC Technical Training Center 920603 2. Dr.R.N.Roy. Text book of biophysics , New central agency (P) Ltd, London . pp 691

3. Valsala Piramal. Biophysics . Dominant publishers and distributers, Newdelhi. 366pp.

4. WWW. Wikipedia.org 5. M.A Subramanian. Biophysics, Principles and practices. MJP publications, Chennai, 324 pp.