Linear Energy Transfer and Relative Biological Effectiveness Ji-Hong Hong, M.D., Ph.D.Ref: Eric J. Hall, Radiobiology for the Radiologist, 5th Edition
Densely vs. Sparsely ionizingSparsely ionizing: ionizing events are well separately in thespace, like: X-ray
Sparsely ionizing radiationTime
High dose sparsely ionizing radiation Time
PhotonProton HeliumCarbon OxygenNeon
The Spatial Distribution of Ionizing Events Varieswith the Type of Radiation and can be defined by LET Separation of ion clusters in relation to LOW LET size of biological target Radiation gamma rays deep therapy X-rays soft X-rays alpha-particle HIGH LET 4 nm Radiation
LET: Linear Energy TransferQuantity: Dose Energy/mass (1 Gy = 1 J/Kg)Quality: LET, Energy/unit length of tract (dE/dl,KeV/µm). Related to mass, energy and chargeof particle.
Typical LET Values
RBE: Relative Biological effectivenessRBEt=D250/Dt (same biological end-point,therefore it is end-point dependent)Reference: 250 kV x-ray
Example• To achieve 50% survival fraction, 250 kV x-ray needs 2 Gy, but the tested particle needs 0.66 Gy onlyRBE = D250/Dt 2 = 2 / 0.66 = 3RBE at survival fraction of 0.5 for the tested particle is 3.
Physical dose vs. biological dose:Same physical dose by different types ofradiation produce different biologicaleffects.
RBE is end-point dependentSurvival curve of split dose experiment: repeated shoulder
RBE is end-point dependentFractionated doses of dense vs. sparse ionizing beam: The RBE of high LET beam becomes larger whenthe fraction number is increasing.
RBE &fractionated doses•For densely ionizing beam: such as neutron –Relatively less sparing effect by fractionated treatment. –The RBE for neutron is relatively large (=3) when the end- point is set as the survival at the shoulder region of x-ray survival curve. – The RBE decreases as the end-point is set as lower survival.
RBE for different cells and tissues•Variation of radiosensitivity between different cell linesand tissues: becomes less when using neutron.2. For cells with large shoulder in survival curve of X-ray: a high RBE for neutron
RBE as a function of LETIncrease of LET from the X-ray to alpha particle:• Smaller shoulder.•Survival curve becomes steeper.
RBE as a function of LET 8 RBE(for cell kill) Fast Alpha 6 Neutrons Particles overkill 4 RBE 2 Co-60 Diagnostic gamma rays X-rays 0 0.1 1 10 100 1000 Linear Energy Transfer (LET keV/mm))
The spatial distributionof ionizing eventsvaries with the type ofradiation and can bedefined by LET. 100 keV/µm RBE LET
RBE as a function of LET• LET > 10 keV/µm Significant increase of RBE.• LET of neutrons, α-particles and other heavy ions > 10keV/µm High RBE.•LET of protons < 10 keV/µm similar RBE to x-ray.
High RBE and cellular repairHigh LET (RBE) beam: less or even no sublethaland potential lethal damage repair.
RBE and OER• Oxygen is a powerful oxidizing agent and therefore acts as a radiosensitizer if it is present at the time of irradiation (within µsecs).• Its effects are measured as the oxygen enhancement ratio (O.E.R.) – O.E.R. = the ratio of doses needed to obtain a given level of biological effect under anoxic and oxic conditions. – O.E.R. = D(anox)/D(ox) O.E.R.= 2.67 – For low LET radiation the O.E.R. is 2.5-3.0 – It is in the higher range at higher doses 1.0 S.F. – For neutrons, O.E.R is about 1.6 hypoxic oxic 0.1 0.01 0 2 4 6 8 10 Dose (Gy)
RBE and OER as a function of LET 8 4 RBE Fast Alpha OER(for cell kill) 6 Neutrons Particles 3 overkill 4 2 RBE 2 Co-60 Diagnostic OER 1 gamma rays X-rays 0 0.1 1 10 100 1000 0 Linear Energy Transfer (LET keV/mm))OER is the inverse of RBE because it depends on theindirect action of ionizing radiation
LET, RBE and OER
Summary of factors that determine RBE •Radiation quality (LET) •Radiation dose •Number of dose fractions •Dose rate •Biological system or end-point
Absorption of neurtons• Elastic scattering – mainly with the hydrogen nuclei, produce recoil proton with high LET (linear energy transfer). • Similar mass, a large proportion of energy is transferred. • Hydrogen is the most abundant amount in tissues. • The collision cross-section (probability) for hydrogen is large.
Why neutrons did not clinically work well •No physical advantage •No selection between normal and tumor cells
Absorption of neurtons• Spallation products – eg. Neutron interact with a carbon, producing α-particles
Why uses heavy ion Bragg peak Spread of Bragg Peak (SOBP) Biological as well as physical advantage
RBE significantly varied with depth. Use physical dose to compensate the biological variation.Biological dose as theprescribed dose
Why use proton?•No biological advantage:RBE: 1.0-1.2•Mainly physical advantages: Bragg Peak andSpread of Bragg peak