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