Radiobiology Hall 7: LET and RBE (Completed)

As LET increases, RBE increases gradually until what value?

10 keV/um

As LET increases, RBE increases drastically from what value until what value?

10 keV/um to 100 keV/um

As LET increases, RBE increases until it peaks out at ______ keV/um?

100 keV/um

X rays are used as the comparison when determining the Relative Biologic Effectiveness (RBE). What is the energy of the x rays that are used as comparison?

250 keV

What is absorbed dose and what is the unit of measure?

A measure of the energy absorbed per unit mass of tissue. gray (Gy)

As the LET increases: the survival-curve becomes (shallower/steeper) and the shoulder of the curve becomes progressively (smaller/larger)

Curve becomes steeper Shoulder becomes smaller

The higher the RBE, the (lower/higher) the killing power?

Higher --------- Because if it takes 5 Gy of x rays to a surviving fraction of 0.01 but only 1 Gy of neutrons then... RBE = 5 VS. If it takes 2 Gy of x rays to a surviving fraction of 0.001 and the same 1 Gy of neutrons then... RBE = 2 Thus... more killing radiation comes from those with HIGHER RBE.

For a given type of charged particle, the higher the energy, the (lower/higher) the LET and, therefore, the (lower/higher) its biologic effectiveness?

Higher energy = Lower LET Lower biologic effectiveness

As LET increases, RBE (decreases/increases)?

Increases slowly at first (until LET 10 keV/um) Increases quickly between LET 10 - 100 keV/um Peaks at 100 keV/um After 100 it falls again beyond that

The survival curve for x-rays has a large initial shoulder; for fast neutrons, the initial shoulder is smaller and the final slope is steeper. Because the survival curves have different shapes, the relative biologic effectiveness (RBE) does not have a unique value but varies with dose. The RBE tends to get (smaller/larger) as the size of the dose is reduced with a SINGLE DOSE?

Larger Larger surviving fraction = less killing = lower doses = larger RBE

The survival curve for x-rays has a large initial shoulder; for fast neutrons, the initial shoulder is smaller and the final slope is steeper. Because the survival curves have different shapes, the relative biologic effectiveness (RBE) does not have a unique value but varies with dose. The RBE tends to get (smaller/larger) as the surviving fraction is increased with a SINGLE DOSE?

Larger Larger surviving fraction = less killing = lower doses = larger RBE

RBE varies greatly according to the tissue or cell line studied. Different cells or tissues are characterized by x-ray survival curves that have large but variable shoulder regions, whereas the shoulder region for neutrons is smaller and less variable. As a consequence, the RBE is different for each cell line. In general, cells characterized by an x-ray survival curve with a large shoulder show (smaller/larger) RBEs for neutrons?

Larger The larger the shoulder for x ray = the larger the RBE

If the objective is to improve killing of a cell population, then the wider the shoulder is on a cell-survival curve, the (less/more) "wasted" dose there is?

More Larger/wider shoulder means less killing and thus if the objective is to kill, then higher doses need to be used and this means there is more "wasted" dose.

Neutrons become progressively (less/more) efficient than x rays for cell killing as the dose per fraction is reduced and the number of fractions is increased?

More Less shoulder on neutrons than x rays which means each fractionation results in less and less "wasted" dose when compared with x rays.

X rays become progressively (less/more) efficient than neutrons for cell preservation as the dose per fraction is reduced and the number of fractions is increased?

More (for CELL SURVIVAL) More shoulder on x rays than neutrons which means each fractionation results in MORE and MORE "wasted" dose or CELL SURVIVING when compared with neutrons.

Describe how number of dose fractions effects the RBE?

RBE depends on the dose level and the number of dose fractions (or, alternatively, the dose per fraction) because in general the shape of the dose-response relationship varies for radiations that differ substantially in their LET

Describe how radiation dose effects the RBE?

RBE depends on the dose level and the number of dose fractions (or, alternatively, the dose per fraction) because in general the shape of the dose-response relationship varies for radiations that differ substantially in their LET

Describe how the biologic system or end point effects the RBE?

RBE is higher for tissues that accumulate and repair a great deal of sublethal damage RBE is low for those that don't

Describe how radiation quality (LET) effects the RBE?

Radiation quality includes the type of radiation and its energy, whether electromagnetic or particulate, and whether charged or uncharged.

In comparing different radiations, it is customary to use x rays as the standard. What is the term used to describe this comparison?

Relative Biologic Effectiveness

SUMMARY: The radiation weighting factor (WR) depends on LET and is specified by the ICRP as a representative RBE at low dose and low dose rate for biologic effects relevant to radiation protection, such as cancer induction and heritable effects. It is used in radiologic protection to reduce radiations of different biologic effectiveness to a common scale.

SUMMARY: Equivalent dose is the product of absorbed dose and the radiation weighting factor. The unit of equivalent dose is the sievert (Sv) (in the old units, absorbed dose was expressed in rads and equivalent dose was expressed in rem).

SUMMARY: RBE increases with LET to a maximum at about 100 keV/um, thereafter decreasing with higher LET.

SUMMARY: For radiation with the optimal LET of 100 keV/um, the average separation between ionizing events is similar to the diameter of the DNA double helix (2 nm), so that DSBs can be most efficiently produced by a single track.

SUMMARY: LET is the energy transferred per unit length of track. Typical values are 0.2 keV/um for cobalt-60 gamma-rays, 2 keV/um for 250-kV x-rays, 166 keV/m for 2.5-MeV alpha-particles, and 1,000 keV/um for heavy charged particles encountered in space.

SUMMARY: RBE of some test radiation (r) is the ratio D250/Dr, in which D250 and Dr are the doses of 250-kV x-rays and the test radiation, respectively, required to produce equal biologic effect.

SUMMARY: The RBE of high-LET radiations compared with that of low-LET radiations increases as the dose per fraction decreases. This is a direct consequence of the fact that the dose-response curve for low-LET radiations has a broader shoulder than for high-LET radiations.

SUMMARY: RBE varies according to the tissue or end point studied. In general, RBE values are high for cells or tissues that accumulate and repair a great deal of sublethal damage, so that their dose-response curves for x-rays have a broad initial shoulder.

SUMMARY: RBE depends on the following: Radiation quality (LET) Radiation dose Number of dose fractions Dose rate Biologic system or end point

SUMMARY: The OER has a value of about 3 for low-LET radiations, falls when the LET rises more than about 30 keV/um and reaches unity by an LET of about 200 keV/um.

SUMMARY: X rays and gamma rays are said to be sparsely ionizing because along the tracks of the electrons set in motion, primary ionizing events are well separated in space.

SUMMARY: alpha-particles and neutrons are densely ionizing because the tracks consist of dense columns of ionization.

What is the unit for equivalent dose?

Sievert (Sv) old term = Rem

The survival curve for x-rays has a large initial shoulder; for fast neutrons, the initial shoulder is smaller and the final slope is steeper. Because the survival curves have different shapes, the relative biologic effectiveness (RBE) does not have a unique value but varies with dose. The RBE tends to get (smaller/larger) as the size of the dose is increased with a SINGLE DOSE?

Smaller Smaller surviving fraction = more killing = higher doses = smaller RBE

The survival curve for x-rays has a large initial shoulder; for fast neutrons, the initial shoulder is smaller and the final slope is steeper. Because the survival curves have different shapes, the relative biologic effectiveness (RBE) does not have a unique value but varies with dose. The RBE tends to get (smaller/larger) as the surviving fraction is reduced with a SINGLE DOSE?

Smaller Smaller surviving fraction = more killing = higher doses = smaller RBE

RBE varies greatly according to the tissue or cell line studied. Different cells or tissues are characterized by x-ray survival curves that have large but variable shoulder regions, whereas the shoulder region for neutrons is smaller and less variable. As a consequence, the RBE is different for each cell line. In general, cells characterized by an x-ray survival curve with a little or nearly no shoulder show (smaller/larger) RBEs for neutrons?

Smaller The smaller the shoulder for x ray = the closer it resembles the "small" shoulder of neutrons

Define the term Relative Biologic Effectiveness?

The RBE of some test radiation (r) compared with x rays is defined by the ratio D250/Dr D250 - dose of x rays Dr - test radiation required for equal biologic effect.

Define Linear Energy Transfer (LET)?

The energy transferred per unit length of track. International Commission on Radiological Units: The LET (L) of charged particles in medium is the quotient of dE/dl dE = the average energy locally imparted to the medium by a charged particle of specified energy in traversing a distance of dl

Describe how radiation dose rate effects the RBE?

The slope of the dose-response curve for sparsely ionizing radiations, such as x or gamma rays, varies critically with a changing dose rate. Biologic response to densely ionizing radiations depends little on the rate at which the radiation is delivered.

How are the weighting factors determined?

They are chosen by the ICRP based on a consideration of experimental RBE values, biased for biologic end points relevant to radiation protection, such as cancer and heritable effects, and also relevant to low doses and low dose rate. There is a considerable element of judgment involved.

LET is an average quantity because at the microscopic level, the energy per unit length of track varies over such a wide range. There are two commonly used methods to calculate the average for LET. Describe each of the following methods? Track average Energy average

Track average -obtained by dividing the track into equal lengths, calculating the energy deposited in each length, and finding the mean. Energy average -obtained by dividing the track into equal energy increments and averaging the lengths of track over which these energy increments are deposited. HINT: The term used with average (Track vs Energy) is the component that is set at equal amounts... Energy average - energy is divided equally and track measured Track average - track is divided equally and energy measured

True or False: More densely ionizing radiation than 100 keV/um is just as effective per track than 100 keV/um, but less effective per unit dose?

True

True or False: More densely ionizing radiation than 100 kev/um has a lower RBE than at 100 keV/um?

True

True or False: The most biologically effective LET is that at which the DNA helix and the average separation of ionizing events are the same?

True

True or False: The radiation weighting factor is set at unity for all low-LET radiations (x rays, gamma rays, and electrons), with a value of 20 for maximally effective neurtrons and alpha-particles.

True

True or False: The spacial distribution of the ionizing events produced by different particles varies enormously due to the difference in the charge-to-mass ratio of differing radiation types.

True

How is the equivalent dose calculated?

Weighting Factor (X) Absorbed Dose = Equivalent Dose

If the objective is to improve survival of a cell population, then the (narrower/wider) the shoulder is on a cell-survival curve, the better?

Wider Larger/wider shoulder means less killing and thus if the objective is to preserve, then wider shoulders are better.

What is the unit for Linear Energy Transfer (LET)?

keV/um ... of unit density material kiloelectron volt per micrometer

As LET increases, RBE increases gradually until 10 keV/um, then drastically from 10 keV/um to 100 keV/um. What happens after an LET value of 100 keV/um

the RBE begins to fall again

Solve: An absorbed dose of alpha particles was 0.1 Gy. What would be the equivalent dose?

Absorbed dose = 0.1 Gy Weighting factor (alpha particle) = 20 0.1 x 20 = 2 Sv Equivalent dose of 2 Sv

RBE depends on which of the following factors? Biologic system or end point Dose Number of dose fractions Radiation dose Radiation quality (LET)

All the above: Biologic system or end point Dose Number of dose fractions Radiation dose Radiation quality (LET)

Why is 100 keV/um the peak or optimal LET?

Because the average separation between ionizing events at 100 keV/um just about coincides with the diameter of the DNA double helix (20 A or 2 nm) Radiation with this density of ionization has the highest probability of causing a double-strand break (DSB) by the passage of a charged particle. DSBs are the basis of most biologic effects.

There is a simpler way to consider differences in biologic effectiveness of different radiations and is done with the Radiation Weighting Factor. What is calculated by multiplying the weighting factor by the absorbed dose?

Equivalent dose

True or False: Equal doses of different types of radiation produce equal biological effects?

False Equal doses of different types of radiation DO NOT produce equal biologic effects.

What is the unit for absorbed dose?

Gray (Gy) old term = Rad

The larger shoulder that is characteristic of the x-ray curve must be repeated for each fraction. This explains the fact that the RBE for a fractionated regimen with neutrons is (smaller/greater) than for a single exposure?

Greater

The RBE for a fractionated regimen with neutrons is (smaller/greater) than for a single exposure?

Greater A fractionated schedule consists of several small doses AND RBE is large for small doses