Linear Energy Transfer and

Relative Biological Effectiveness

Ji-Hong Hong, M.D., Ph.D.
Ref: Eric J. Hall, Radiobiology for the Radiologist, 5
th
Edition
Densely vs. Sparsely ionizing

Sparsely ionizing: ionizing events are well separately in the
space, like: X-ray
T
i
m
e

Sparsely ionizing radiation
High dose sparsely ionizing radiation
T
i
m
e

Photon

Proton

Helium


Carbon


Oxygen


Neon

gamma rays

deep therapy
X-rays

soft X-rays


alpha-particle
HIGH LET
Radiation
LOW LET
Radiation
Separation of ion clusters in relation to
size of biological target
4 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/mm).
Related to mass, energy and charge
of particle.
Typical LET Values
RBE: Relative Biological effectiveness
RBE
t
=D
250
/D
t
(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 only

RBE = D
250
/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))
RBE
(for cell kill)
1000 100 10 1
0
2
4
6
8
RBE
Diagnostic
X-rays
Fast
Neutrons
Alpha
Particles
overkill
0.1
Co-60
gamma rays
RBE
LET
100 keV/mm
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/mm Significant increase of RBE.
LET of neutrons, a-particles and other heavy ions > 10
keV/mm High RBE.
LET of protons < 10 keV/mm 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
radiosensitizer if it is present at the time of irradiation (within
msecs).
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)
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)
O.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))
RBE
(for cell kill)
1000 100 10 1
0
2
4
6
8
RBE
Diagnostic
X-rays
Fast
Neutrons
Alpha
Particles
overkill
0.1
Co-60
gamma rays
0
1
2
3
4
OER
OER
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 a-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