L3 Linear Energy Transfer (LET) and Relative Biological Efficiency (RBE) Linear energy transfer (LET) It describes how much energy an ionizing particle transfers to the material (transverse per unit distance). Or the amount of energy a radiation deposits per unit of path length (i.e., kilo electron volts/micron - Kev/µm).It describes the action of radiation into matter. LET is a positive quantity, depends on the nature of the radiation as well as on the material traversed. LET increases with the square of the charge on the incident particle. When ionizing radiation interacts within cells, it deposits ionizing energy in the cell .The higher the charge of the particle and the lower the velocity, the greater likelihood to produce ionization. Linear energy transfer (LET) A measure of the rate at which energy is transferred from ionizing radiation to soft tissue Mass, charge and velocity of a particle all affect the rate at which ionization occurs and is related to range. (Heavy, highly charged particles (e.g., α-particle) lose energy rapidly with distance and do not penetrate deeply. In general, radiation with a long range (e.g., x-/γ-rays, high energy ß- particles) usually has a low LET, While large particulate radiations with short range (e.g., α-particles, neutrons, protons) have a high LET. • LET is number of ionizations which radiation causes per unit distance as it traverses the tissue • Medical x-rays and gamma rays are low LET. LET of diagnostic x-rays is 3.0 • Alpha particles are high LET - about 100.0 • LET varies with type of radiation • LET is potential ionization Relative Biologic Effectiveness, RBE It is the ratio of biological effectiveness of one type of ionizing radiation relative to another, given the same amount of absorbed energy. The RBE is an empirical value that varies depending on the particles, energies involved, and which biological effects are deemed relevant. The higher the RBE of radiation, the more damaging is the type of radiation, per unit of energy deposited in biological tissues. Different types of radiation have different biological effectiveness because they transfer their energy to the tissue in different ways In tissue, the biologic effect of a radiation depends upon the amount of energy transferred to the tissue volume or critical target (i.e., the amount of ionization) and is therefore a function of LET. Higher LET , higher ability to produced damage In radiation biology research, many different types and energies of radiation are used and it become difficult to compare the results of the experiments based solely on LET a more general term, the relative biologic effectiveness , RBE, was developed 1 In using RBE ,it has become customary to use either 250 keV x-rays or 1.17/1.33 MeV 60Co gamma rays. as the standard reference radiation . The formula definition is : RBE = for a given effect For example ,if 10 Gy of 60Co gamma rays kills 50 % of the mice in a group, and 1 Gy of heavy ion radiotherapy kills the other group, the RBE would be: RBE= =10/1 =10 RBE is initially proportional to LET and, as the LET for ionizing radiation increases, so does the RBE. For low LET radiation, RBE LET, for higher LET the RBE increases to a maximum, the subsequent drop is caused by the overkill effect. Quality Factor (QF) (weighting factors) Different types of radiation do different amounts of biological damage, Quality factor of the radiation a factor express the effectiveness of the absorbed dose; for ease of calculation, the QF of most of the radiation are: Gamma Rays =1, Alpha Particles =20 X-rays =1, Thermal Neutron =3 β- Particles =1, Fast Neutron =10 The Quality Factor is used to modify the Absorbed Dose in Gray (Gy) by multiplying to obtain a quantity called the Equivalent Dose Equivalent Dose = Quality Factor(RBE)* Absorbed Dose Dequiv = RBE x Dabs Radiation dosimetry is the quantitative description of the effect of radiation on living tissue . Absorbed dose is a measure of the energy deposited in an irradiated medium by ionizing radiation per unit mass. Absorbed dose is used in the calculation of dose uptake in living tissue in both radiation protection (reduction of harmful effects), and radiology (potential beneficial effects for example in cancer treatment). It is also used to directly compare the effect of radiation on inanimate matter. The SI unit of measure is the gray (Gy), which is defined as one Joule of energy absorbed per kilogram of matter The biological effect of the absorbed dose in tissue cells depends on the type of radiation . 2 The SI unit of the absorbed dose is the Joule/kilogram or the gray (Gy:)1Gy = 1J/kg .We use also other unit as the rad : 1Gy = 100 rad . The units Sievert (Sv ,)and rem: röntgen equivalent man : Dequiv(Sv) = RBE x Dabs( Gy ( Dequiv)rem)= RBE x Dabs )rad) With 1 Gy = 100 rad, we have 1Sv = 100rem . The unit of the RBE is Sv/Gy = rem/rad It is used because some types of radiation, such as Alpha Particles , are more biologically damaging internally than other types such as the Beta Particle . Low energy (Emax < 0.03 MeV) particles have a QF of 1.7 which reflects their inability to travel far in biological tissues and their resulting tendency to dissipate all their energy locally and therefore to cause greater biological damage. Photons and beta particles have a low linear energy transfer coefficient, meaning that they ionize atoms in the tissue that are spaced by several hundred nanometers (several tenths of a micrometer) apart, along their path Radiation weighting factors(QF) that go from physical energy to biological effect must not be confused with tissue weighting factors. The tissue weighting factors are used to convert an equivalent dose to a given tissue in the body, to an effective radiation dose, Effective radiation dose, a number that provides an estimation of total danger to the whole organism, as a result of the radiation dose to part of the body. The oxygen enhancement ratio (OER) OER : is the ratio of doses under hypoxic to aerated conditions that produce the same biologic effect. Or OER detrimental effect of ionizing radiation due to the presence of oxygen. The presence or absence of molecular oxygen dramatically influences the biologic effect of x- rays. Oxygen presence (aerated cells) increases radiation effectiveness for cell killing. Lack of oxygen (hypoxic cells) results in more radio resistant cells. ORE = The maximum OER depends mainly on the ionizing density or LET of the radiation. Radiation with higher LET and higher relative biological effectiveness (RBE) have a lower OER in mammalian cell tissues . The value of the maximum OER varies from about 1-4. The maximum OER ranges from about 2-4 for low-LET radiations such as X-rays, beta particles and gamma rays, whereas the OER is unity for high-LET radiations such as low energy alpha particles. 3 Uses in medicine The effect is used in medical physics to increase the effect of radiation therapy in oncology treatments. − Additional oxygen abundance creates additional free radicals(superoxide O2 , hydrogen peroxide H2O2 )and increases the damage to the target tissue(DNA damage). In solid tumors the inner parts become less oxygenated than normal tissue and up to three times higher dose is needed to achieve the same tumor control probability as in tissue with normal oxygenation. Radiation therapy The measurement of absorbed dose in tissue is of fundamental importance in radiobiology as it is the measure of the amount of energy the incident radiation is imparting to the target tissue. Radiation therapy or radiotherapy, RT, is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer). Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. 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 cancerous tissue leading to cellular death. To spare normal tissues (such as skin or organs which radiation must pass through to treat the tumor), shaped radiation beams are aimed from several angles of exposure to intersect at the tumor, providing a much larger absorbed dose there than in the surrounding, healthy tissue. 4 .