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

Time

Sparsely ionizing radiation

Time

High dose sparsely ionizing radiation

Photon
Proton
Helium
Carbon
Oxygen
Neon

The Spatial Distribution of Ionizing Events Varies

with the Type of Radiation and can be defined by LET
Separationofionclustersinrelationto
sizeofbiologicaltarget

LOWLET
Radiation
gammarays
deeptherapy
Xrays
softXrays
alphaparticle

4nm

HIGHLET
Radiation

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,
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 = 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 endpoint 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 Xray: 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

8

RBE

Fast
Alpha
Neutrons Particles

(forcellkill)

overkill

4
2
0

RBE
Co60 Diagnostic
gammarays Xrays
0.1

10

100

LinearEnergyTransfer(LETkeV/mm))

1000

The spatial distribution

of ionizing events
varies with the type of
radiation and can be
defined by LET.

100 keV/m

RBE
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
radiosensitizer 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
biological effect under anoxic and oxic conditions.
O.E.R.=2.67
O.E.R. = D(anox)/D(ox)
For low LET radiation the O.E.R. is 2.5-3.0
1.0
It is in the higher range at higher doses
S.F.
For neutrons, O.E.R is about 1.6
hypoxic
oxic
0.1

0.01
0246810
Dose(Gy)

RBE and OER as a function of LET

RBE

4
Fast
Neutrons

(forcellkill)6

Alpha
Particles

overkill

4
2

OER

RBE
Co60
Diagnostic
gammarays Xrays

0 0.1

10

OER
100

2
1

1000 0

LinearEnergyTransfer(LETkeV/mm))

OERistheinverseofRBEbecauseitdependsonthe
indirectactionofionizingradiation

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

RBE significantly varied

with depth.
Use physical dose to
compensate the
biological variation.

Biological dose as the

prescribed dose

Why use proton?

No biological advantage:
RBE: 1.0-1.2
Mainly physical advantages: Bragg Peak and
Spread of Bragg peak