05 linear energy transfer
TRANSCRIPT
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 ionizing Sparsely ionizing: ionizing events are well separately in the space, like: X-ray
Tim
eSparsely ionizing radiation
High dose sparsely ionizing radiation
Tim
e
Photon
Proton
Helium
Carbon
Oxygen
Neon
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
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.
Typical LET Values
RBE: Relative Biological effectiveness
RBEt=D250/Dt (same biological end-point, the
refore 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 only
RBE = D250/Dt 2 = 2 / 0.66 = 3
RBE at survival fraction of 0.5 for the tested particle is 3.
Physical dose vs. biological dose:
Same physical dose by different types of radiation produce different biological effects.
RBE is end-point dependent
Survival curve of split dose experiment: repeated shoulder
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.
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 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
RBE as a function of LET
Increase of LET from the X-ray to alpha particle:• Smaller shoulder.•Survival curve becomes steeper.
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
RBE
LET
100 keV/m
The spatial distribution of ionizing events varies with the type of radiation and can be defined by LET.
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.
High RBE and cellular repair
High LET (RBE) beam: less or even no sublethal and potential lethal damage repair.
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
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
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 -particles
Why uses heavy ion
Bragg peak
Spread of Bragg Peak (SOBP)
Biological as well as physical advantage
Biological dose as the prescribed dose
RBE significantly varied with depth.
Use physical dose to compensate the biological variation.
Why use proton?
•No biological advantage:RBE: 1.0-1.2
•Mainly physical advantages: Bragg Peak and Spread of Bragg peak