LET, RBE & OER - dr vandana

OER, LET and RBE

Presented By:

Vandana (JR-II)

Dept. of Radiotherapy

CSMMU, Lucknow

Moderated By:

• Mr. Teerthraj

• Dr. Jitendra Verma

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Oxygen Enhancement Ratio (OER)

8/28/2011Presented by: Dr. Vandana, CSMMU, Lucknow

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OER

• The oxygen enhancement ratio (OER) is the ratio ofdoses under hypoxic to aerated conditions thatproduce the same biologic effect.

• The presence or absence of molecular oxygendramatically influences the biologic effect of x-rays.

• Oxygen presence (aerated cells) increases radiationeffectiveness for cell killing.

• Lack of oxygen (hypoxic cells) results in more radioresistant cells.


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Nature of the Oxygen Effect

8/28/2011Presented by: Dr. Vandana, CSMMU, Lucknow 4

Su

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Fra

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on

Cells are much more sensitive to x-rays in the presence of molecular oxygen than inits absence (i.e., under hypoxia). The ratio of doses under hypoxic to aeratedconditions necessary to produce the same level of cell killing is called the oxygenenhancement ratio (OER).

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Oxygen Effect


To produce its effect,molecular oxygen mustbe present during theradiation exposure orat least during thelifetime of the freeradicals generated bythe radiation.

Oxygen “fixes” (i.e., makes permanent) the damage produced by free radicals.

In the absence of oxygen, damage produced by the indirect action may be repaired.

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Oxygen Fixation


CH3

functional

group

CH2•

free radical,

unpaired electron

Generally, the free-radical reactions go like this:

CH2• + O2 CH2O2

an organic peroxide “fixes” the indirect damage

ion pairs

free radicals

(oxygen has no impact on direct damage)

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Radio-sensitivity and O2 Concentration

Most of the change ofsensitivity occurs as theoxygen tension increasesfrom 0 to 30 mm Hg.

A further increase ofoxygen content has littlefurther effect.

A relative radio-sensitivityhalfway between anoxiaand full oxygenationoccurs for a pO2 of about 3mm Hg, whichcorresponds to aconcentration of about0.5% oxygen.

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Fig: The dependence of radio-sensitivity on oxygen concentration

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OER Effect

OER varies from 2-3, increasing with dose

Low-LET radiations

oxygen effect is more pronounced

High-LET radiations

oxygen effect is non-existent (OER = 1)


Low-LET radiation

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Other Radiations and the OER


0.001

0.01

Dose, Gy

0.001

0.1

0.01

1.0

1.0 2.00 3.0

Dose, Gy

particles

OER = 1.0

0.1

1.0

0 62 4

OER = 1.6

15 MeV Neutrons

Hypoxic

Aerated

High-LET radiation

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Linear Energy Transfer (LET)


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LET

LET can be defined as “The energy deposited per unit track”

Unit is KeV/ m

The linear energy transfer (LET) of charged particles in the medium isthe quotient of dE/dx, where dE is the average energy locally impartedto the medium by a charged particle in traversing a distance of dx.


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dispersion of energy

low LET ( , x, ~ )

high LET ( , n, p)

air tissue

inci

den

t ra

dia

tio

n

greater radiotoxicity

LET = linear energy transfer

On the following diagram, each dot represents a unit of energy deposited. As you see: Alpha particles impart a large amount ofenergy in a short distance (denselyionizing). Beta particles impart less energy than alpha, but are more penetrating. Gamma rays impart energy sparsely and are the most penetrating.

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Typical LET values


Radiation Linear Energy Transfer ( keV/µm )

Cobalt-60 γ-rays 0.2

250-kV x-rays 2.0

10-MeV protons 4.7

150-MeV proton 0.5

14-MeV neutrons Track Avg. 12 Energy Avg. 100

2.5-MeV α-particles 166

2-GeV Fe ions (space radiation )

1000

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The Optimal LET


LET of about 100 keV/μm isoptimal in terms of producing abiologic effect.

At this density of ionization, theaverage separation in ionizing eventsis equal to the diameter of DNAdouble helix which causes significantDouble Strand Breaks(DSBs). DSBsare the basis of most biologic effects.

The probability of causing DSBs islow in sparsely ionizing radiationsuch as x-rays that has a low RBE.

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Effect of LET on cell survival

Fig: Survival curves for cultured cells of human origin exposed to 250-kV X-rays,15-MeVneutrons, and 4-MeV alpha-particles. As the LET of the radiation increases, the survival curvechanges: the slope of the survival curves gets steeper and the size of the initial shoulder getssmaller.

16 8/28/2011Presented by: Dr. Vandana, CSMMU, Lucknow

Fig. :Oxygen enhancement ratio as a function of linear energy transfer.

At low LET, corresponding to x- or γ-rays, the OER is between 2.5 and 3; As the LET increases, the OER falls slowly at first, until the LET exceeds about 60 keV/µm,after which the OER falls rapidly and reaches unity by the time the LET has reached about 200keV/µm

OER and LET

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Relative Biologic Effectiveness (RBE)


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In comparing different type of radiations, x-rays are used as thestandard. Relative Biologic Effectiveness (RBE) of radiation for producinga given biological effect is given as below:

RBE

Dose in Gy from 250 KeV X-rays Dose in Gy from another radiation source to produce the same biologic response

RBE =

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RBE

The amount or quantity of radiation is expressed in terms of theabsorbed dose, a physical quantity with the unit of Gray or Rad.Absorbed dose is a measure of energy absorbed per unit mass of tissue.

Equal doses of different types of radiation do not produce equal biologiceffects. One gray of neutrons produces a greater biologic effect than 1gray of X-rays.

The key to the difference lies in the pattern of energy deposition.


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Factors that determine RBE

Biologic system or

endpoint

Dose level and the number

of fractions

Dose Rate

Radiation quality (LET)

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Biologic system or endpoint

RBE varies according to the tissueor endpoint studied.

It has a marked influence on theRBE values obtained.

RBE values are high for tissuesthat accumulate and repair a greatdeal of Sub-Lethal Damage (SLD) andlow for those that do not repair SLD.

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RBE for different cells and tissuesFigure below illustrates the difference in intrinsic radiosensitivity among various types of cells:

Fig: Survival curves for varioustypes of Clonogenic mammaliancells irradiated with 300 kV X-raysor 15-MeV neutrons.

Variation in radiosensitivityamong different cell lines ismarkedly less for neutrons thanfor x-rays.

Cells characterized by x-raysurvival curve with a largeshoulder, indicating that theycan accumulate and repair a largeamount of sub-lethal radiationdamage, show larger RBE forneutrons.

Conversely, cells for which x-ray survival curve has little if anyshoulder exhibit smaller neutronRBE values.

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End Point

LD50 of X-rays (250-kV) in causing plant deaths is 6 Gy (600 rad)

LD50 of neutrons in causing plant deaths is 4 Gy (400 rad)

The RBE of neutrons compared with x-rays is then simply the ratio of 6:4which is 1.5.

To measure the RBE of some test radiation, one first choose a biological systemin which the effect of radiations may be scored quantitatively as well as choosean end point.

For Example: If We are measuring the RBE of fast neutrons compared with 250-kV X-rays, using the lethality of plant seedlings as a test system, groups of plantsare exposed to a range of either X-rays or neutron doses.

Note: LD50 is dose of radiation that result in death of half of the plants in a group.

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Figure: shows survival curves obtained ifmammalian cells in culture are exposed toa range of doses of either fast neutrons or250-kV X-rays.

For surviving fraction of .01, RBE =(10 Gy dose of x-rays)/ (6.6 Gy dose of neutrons) = 1.5

For surviving fraction of 0.6, RBE =(3 Gy dose of x-rays)/ (1Gy dose of neutrons) = 3.0

Because the X-rays and neutronsurvival curves have different shapes, theX-ray survival curve having an initialshoulder and the neutron curve being anexponential function of dose, theresultant RBE depends on the level ofdose chosen.

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Dose Level and fractionated doses

For a surviving fraction of 0.01 the RBEfor neutrons relative to X-rays is 2.6(was 1.5 at single exposure). This isdirect consequence of larger shoulderof x-ray curve.

The width of the shoulder represents apart of the dose that is “wasted”; thelarger the number of fractions, thegreater the extent of the wastage.Neutrons curve-almost no shoulder.

Net result is that neutrons becomeprogressively more efficient than x-raysas the dose per fraction is reduced andthe number of fraction is increased.

The RBE generally increases as the dose is decreased.The RBE for a fractionated regimen with neutrons is greater than for a singleexposure, because a fractionated schedule consists of a number of small doses andthe RBE is large for small doses.

Fractionation of radiation dose increases cell

survival

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The lower the doserate, the higher thesurvival.

RBE as a function of dose rate

RBE can vary with the dose rate because the slope of the dose-responsecurve for sparsely ionizing radiations, such as x- or γ-rays, varies criticallywith a changing dose rate. In contrast, the biologic response to denselyionizing radiations depends little on the rate at which the radiation isdelivered.

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RBE as a function of LET

Beyond this value for the LET, the RBE again falls to lower values.

The LET at which the RBE reachesa peak is much the same (about 100keV/μm) for a wide range ofmammalian cells.

As the LET increases, the RBEincreases slowly at first, and thenmore rapidly as the LET increasesbeyond 10 keV/ μm.

Between 10 and 100 keV/ μm, theRBE increases rapidly with increasingLET and reaches the maximum atabout 100 keV μm.

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In the case of sparsely ionizing X-rays the probability of a single track causing a DSB is low, thus X-rays have a low RBE. At the other extreme, densely ionizingradiations (ex. LET of 200 keV/ μm) readily produce DSB, but energy is “wasted”because the ionizing events are too close together. Thus, RBE is lower than optimal LET radiation.

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OER & RBE as a function of LET


Fig: Variation of OER andRBE as a function of LET ofthe radiation involved.

Variation of the OER and the RBE as a function of LET. The two curves are virtually mirror image of each other. The optimal RBE and the rapid fall of OER occur at about the same LET value, 100 keV/µm

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Conclusion• OER is the ratio of hypoxic-to-aerated doses

• OER decreases as LET increases

• Oxygen must be present during irradiation, or very soon after (microseconds)

• Only a small of amount O2 is required (< 5%)

• LET – energy transferred per unit length of track

• Densely ionizing radiation – High LET, Sparsely ionizing radiation – Low LET


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• Optimal LET is 100 keV/μm

• OER reaches unity by an LET of about 200 kev/μm

• Relative biologic effectiveness (RBE) is the ratio D250/Dr

• For low LET radiation, RBE LET, for higher LET the RBE increases to a maximum, the subsequent drop is caused by the overkill effect.

• RBE is large for small doses.

• RBE values are higher for tissues that repair SLD.


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Thank You

LET, RBE & OER - dr vandana

Health & Medicine

Transcript of LET, RBE & OER - dr vandana