05 linear energy transfer
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Linear Energy Transfer and Relative Biological Effectiveness
Ji-Hong Hong, M.D., Ph.D.
Ref: Eric J. Hall, Radiobiology for the Radiologist, 5th Edition
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Densely vs. Sparsely ionizing Sparsely ionizing: ionizing events are well separately in the space, like: X-ray
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Tim
eSparsely ionizing radiation
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High dose sparsely ionizing radiation
Tim
e
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Photon
Proton
Helium
Carbon
Oxygen
Neon
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gamma raysgamma rays
deep therapydeep therapyX-raysX-rays
soft X-rayssoft X-rays
alpha-particlealpha-particle
HIGH LETHIGH LETRadiationRadiation
LOW LETLOW LETRadiationRadiation
Separation of ion clusters in relation toSeparation of ion clusters in relation tosize of biological targetsize of biological target
4 nm4 nm
The Spatial Distribution of Ionizing Events Varies with the Type of Radiation and can be defined by LET
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LET: Linear Energy Transfer
Quantity: Dose
Energy/mass (1 Gy = 1 J/Kg)
Quality: LET,
Energy/unit length of tract (dE/dl, KeV/m).
Related to mass, energy and charge of particle.
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Typical LET Values
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RBE: Relative Biological effectiveness
RBEt=D250/Dt (same biological end-point, the
refore it is end-point dependent)
Reference: 250 kV x-ray
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Example
• To achieve 50% survival fraction, 250 kV x-ray needs 2 Gy, but the tested particle needs 0.66 Gy only
RBE = D250/Dt 2 = 2 / 0.66 = 3
RBE at survival fraction of 0.5 for the tested particle is 3.
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Physical dose vs. biological dose:
Same physical dose by different types of radiation produce different biological effects.
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RBE is end-point dependent
Survival curve of split dose experiment: repeated shoulder
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RBE is end-point dependent
Fractionated doses of dense vs. sparse ionizing beam:
The RBE of high LET beam becomes larger when the fraction number is increasing.
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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.
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RBE for different cells and tissues
•Variation of radiosensitivity between different cell lines and tissues: becomes less when using neutron.2. For cells with large shoulder in survival curve of X-ray: a high RBE for neutron
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RBE as a function of LET
Increase of LET from the X-ray to alpha particle:• Smaller shoulder.•Survival curve becomes steeper.
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RBE as a function of LET
Linear Energy Transfer (LET keV/mm))Linear Energy Transfer (LET keV/mm))
RBERBE(for cell kill)(for cell kill)
1000100010010010101100
22
44
66
88
RBERBE
DiagnosticDiagnosticX-raysX-rays
Fast Fast NeutronsNeutrons
Alpha Alpha ParticlesParticles
overkilloverkill
0.10.1
Co-60Co-60gamma raysgamma rays
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RBE
LET
100 keV/m
The spatial distribution of ionizing events varies with the type of radiation and can be defined by LET.
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RBE as a function of LET
• LET > 10 keV/m Significant increase of RBE.
• LET of neutrons, -particles and other heavy ions > 10 keV/m High RBE.
•LET of protons < 10 keV/m similar RBE to x-ray.
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High RBE and cellular repair
High LET (RBE) beam: less or even no sublethal and potential lethal damage repair.
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RBE and OER• Oxygen is a powerful oxidizing agent and therefore acts as a ra
diosensitizer if it is present at the time of irradiation (within secs).
• 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 biologica
l effect under anoxic and oxic conditions.– O.E.R. = D(anox)/D(ox)– For low LET radiation the O.E.R. is 2.5-3.0– It is in the higher range at higher doses– For neutrons, O.E.R is about 1.6
Dose (Gy)Dose (Gy)
O.E.R.= 2.67O.E.R.= 2.67
S.F.
0 2 4 6 8 10
1.0
0.1
0.01
oxic
hypoxic
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RBE and OER as a function of LET
Linear Energy Transfer (LET keV/mm))Linear Energy Transfer (LET keV/mm))
RBERBE(for cell kill)(for cell kill)
1000100010010010101100
22
44
66
88
RBERBE
DiagnosticDiagnosticX-raysX-rays
Fast Fast NeutronsNeutrons
Alpha Alpha ParticlesParticles
overkilloverkill
0.10.1
Co-60Co-60gamma raysgamma rays
00
11
22
33
44
OEROER
OEROER
OER is the inverse of RBE because it depends on the indirect action of ionizing radiation
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LET, RBE and OER
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Summary of factors that determine RBE
•Radiation quality (LET)
•Radiation dose
•Number of dose fractions
•Dose rate
•Biological system or end-point
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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.
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Why neutrons did not clinically work well
•No physical advantage•No selection between normal and tumor cells
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Absorption of neurtons
• Spallation products– eg. Neutron interact with a carbon, producing -particles
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Why uses heavy ion
Bragg peak
Spread of Bragg Peak (SOBP)
Biological as well as physical advantage
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Biological dose as the prescribed dose
RBE significantly varied with depth.
Use physical dose to compensate the biological variation.
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Why use proton?
•No biological advantage:RBE: 1.0-1.2
•Mainly physical advantages: Bragg Peak and Spread of Bragg peak