Linear Energy Transfer and Relative Biological Effectiveness PDF

Linear Energy Transfer and Relative Biological Effectiveness 1 The Deposition of Radiant Energy 2  The Deposition of Radiant Energy Radiation Absorption of Biologic material Occurrence Ionization...

Linear Energy Transfer and Relative Biological Effectiveness 1 The Deposition of Radiant Energy 2  The Deposition of Radiant Energy Radiation Absorption of Biologic material Occurrence Ionization Excitation Not distributed at random Localized along the tracks of individual charged particle Depends on the types of radiation involved 3  The Deposition of Radiant Energy Examples Photons of x-rays Give rise to fast electrons Particle carrying unit of charge NO mass Neutrons Give rise to recoil protons Particle carrying unit of charge Mass: 2000 x of electrons α-particle Particle carrying 2 electric charge Mass: 4 x of protons, 8000 x of electrons 4  Radiosensitivty of living tissues varies with maturation & metabolism; 1. Stem cells are radiosensitive. More mature cells are more resistant 2. Younger tissues are more radiosensitive 3. Tissues with high metabolic activity are highly radiosensitive 4. High proliferation and growth rate, high radiosensitivty Two identical doses may not produce identical responses due to other modifying factors Factors Affecting Radiation Response are, Physical Factors Biological Factors Linear energy Oxygen Effect transfer Phase of cell Relative cycle biological Ability to Repair effectiveness Chemical Agents Fractionation Hormesis & protraction  Linear Energy Transfer Linear Energy Transfer (LET) is the rate at which energy is deposited as a charged particle travels through matter by a particular type of radiation. Linear Energy Transfer (LET):the energy deposited per unit track. Unit is keV/m.  Particulate radiation: Linear Energy Transfer (LET) Describesdensity of ionization in particle tracks – 1.2 MeV 60Co =0.3 keV/μm; 250 kVp x‐rays=2 keV/μm – 10 MeV p=4.7 keV/μm; 150 MeV p=0.5 keV/μm – 2.5 MeV α=166 keV/μm; 4 MeV α=100 keV/μm As LET increases, morecell killing per Gray – High LET if >10 keV/μm; overkill effect ~100‐150 keV/μm For a given type of particle, the higher the energy, the lower the LET and lower biologicaleffect  With low LET radiation the interactions that are produced are relatively far apart from each other, therefore, they will be spread throughout the cell, making for a more uniform dose distribution throughout the cell. With high LET radiation the particles give rise to well defined tracks of ionization which cause extensive damage along the path.  Low and High LET Radiations Low LET Radiation: – This is a type of ionizing radiation that deposit less amount of energy along the track or have infrequent or widely spaced ionizing events. – Eg. x-rays, gamma rays High LET Radiation: – This is a type of ionizing radiation that deposit a large amount of energy in a small distance. – Eg. Neutrons , alpha particles with the Type of Radiation and can be defined by LET LOW LET Radiation HIGH LET Radiation The background : electron micrograph of human cell The white dot : computer simulate ionizing events Intermediated in ionization density Densely ionizing Sparsely ionizing Sparsely ionizing Variation of ionization density associated with different types of radiation 13  High vs Low LET Radiations High LET radiation ionizes water into H and OH radicals over a very short track. In fig 1, two events occur in a single cell so as to form a pair of adjacent OH radicals that recombine to form peroxide, H2O2, which can produce oxidative damage in the cell. Low LET radiation also ionizes water molecules, but over a much longer track. In fig 2, two events occur in separate cells, such that adjacent radicals are of the opposite type: the H and OH radicals reunite and reform H2O.  LET of about 100 keV/μm is optimal in terms of producing a biologic effect. At this density of ionization, the average separation in ionizing events is equal to the diameter of DNA double helix which causes significant DSBs. DSBs are the basis of most biologic effects. The probability of causing DSBs is low in sparsely ionizing radiation such as x-rays that has a low RBE.  Human fibroblasts Immunostained for detection of ‐H2AX at 10 min post‐RT. Each green focus corresponds to a DNA DSB 0.5Gy 54 keV/µm 0.5 Gy of 176 2 Gy‐rays silicon ions keV/µm iron ions Desai et al., RADIATION RESEARCH 164, 518–522 (2005)  …for a given type of particle, Calculated track the higher the energy, the patterns ‐ LET lower the LET and lower biological effect. MeV 1 Carbon 2 MeV  particle 1 4 6 3 8 H. G. Paretzke, Radiation Track Structure Theory, in Kinetics of Nonhomogeneous Processes, G. R. Freeman (Ed.), Wiley Interscience Publication, New York,1987.  THREEPOPULARESTABLISHED CELL-LINES HeLa Cells (human cancer cells) CHOCells (Chinese hamster ovary cells) V79 Cells (Chinese hamster lung fibroblast cells) 19 HeLa Cells (human cancer cells) 20  CELL DEATH For proliferating cells of an established cell-line, death is defined as reproductive death when cells no longer have the capacity for sustained proliferation and colony formation (clonogenic) Cells may lose reproductive capacity through  Apoptosis  Giant cell formation  Death attempting cell division (mitotic death) For most cultured cells mitotic death is the dominant mode  The fate of cells exposed to radiation Nias Chapter 6  The first mammalian cell survival curve Nias Chapter 8  Survival curves for cultured cells of human origin exposed to 250-kV X- rays, 15-MeV neutrons, and 4-MeV alpha-particles. As the LET of the radiation increases, the survival curve changes: the slope of the survival curves gets steeper and the size of the initial shoulder gets smaller Over the past 50 years many cell lines have been investigated and, apart from their practical value for improving the therapeutic use of radiation, the shape of the survival curve itself helps our understanding of the mechanisms underlying radiation damage Hall Chapter 3  overkill high LET Low LET Barendsen, Curr Top Radiat Res Quart 4:293 (1968)  Single strand breaks (SSBs): Model A complex SSB is defined as a SSB accompanied by another SSB on the same strand or on the opposite strand but too far away to constitute a double‐strand break. ( , ), Protons; ( , ), α particles. Nikjoo et al. Radiat Res. 2001 Nov;156(5 Pt 2):577‐83. 28