Radiobiology Lecture 4 Let & Rbe

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One method of describing the energy transfered by radiation interacting with living tissue is by

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linear energy transfer. Radiation as it passes through matter loses energy through ionizations and excitations. The rate of energy loss depends on the type of radiation.

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Linear Energy Transfer (LET)

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energy transfered per unit track length keV/um)

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It is important to remember that LET is an average.

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The number of ionizations in any short segment of the particle track will vary greatly.

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Low LET

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Sparsely ionizing radiations - photons, X-rays, and low energy electrons.... per unit rate

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Ordinarily Careless / Crappers Are / Also / frivolous About Urination

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ornithine + carbamoyl phosphate -->

citrulline + aspartate -->

arginosuccinate (minus fumarate as by-product) -->

arginine (minus Urea as by product which starts cycle over) --> ornithine

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In general, for a given type of radiation, the higher the energy the lower

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the LET
** Opposite of what you think

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This may seem like it should be the opposite, but we need to keep in mind that a particle traveling

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faster passes right though tissue with little interaction. Ionizations increase in number per unit length as the particles loses energy.

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Higher Energy Radiation has a lower LET

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Quickly passes through mass

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Therefore: Increasing the energy of the radiation, increases the

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distance traveled through matter and decreases the ionization density of LET. However, the overall number of ionizations may be higher.

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Increasing the mass and charge of a particle

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increases the LET

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Traveling through mass so fast without having the time

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to have an negative effect which is good for nuclear medicine, this allows us to safely perform scans!

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The Oxygen Effect & LET

The O2 effect is most significant for sparse, indirectly ionizing radiations like X and gamma rays.

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There is little O2 effect for dense, directly ionizing radiations.

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Therefore, The O2 effect decreases

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with increasing LET

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Relative Biological Effectiveness (RBE)
Absorbed radiation is expressed as dose and is measured in Rads or Grays

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Rads and Grays are units of absorbed energy per mass
Rads = 100ergs/gray

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Different types of radiation do not necessarily have the same biological effect even if the same dose is absorbed.

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For instance, 1 rad of 19 MeV protons will have a grater effect than 1 Rad of Cobalt 60 y rays
250 keV as standard

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Formally, the RBE is a comparison of the biologically effect of some radiation to the biologically effect

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of 250 keV X-rays

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For example, if it takes 100 rads of 250 Kev X-rays to kill half the cells in a culture and only 75 rads of 10 MeV protons to kill half the cells in an identical culture, the RBE =

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100 Rads of 250 Kev X-rays/
75 rads of 10 Mec protons

= 1.3 more effective in killing cells then 250 Kev

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RBE increases with LET to about 100 Kev/um, therefore decreasing with higher LET.

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100 Kev is the optimal LET because it provides an ionization in tissue at a distance of about 2 nm which is the diameter of a DNA double helix. This is efficient at producing double strand breaks with one particle track.

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2 nm

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is the optimal LET cell killing radiation

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The Relationship between RBE & LET
- See P.P

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For values greater than 100 Kev, its not as efficient in cell killing, overkill!!!

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Factors Effecting RBE:

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1. Radiation quality (LET)
2. Radiation Dose
3. Number of Dose Fractions
4. Dose Rate
5. Biological system or endpoint

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As we know, there are many different cell types within the human body,

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the differing cell types have associated.radiosensitivites

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Law of Bergonie & Tribondeau

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Ionizing Radiation is more effective against cells that are actively more mitotic, undifferentiated ( bone marrow, not in hands) divide rapidly and have long dividing future.

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Law of Bergonie & Tribondeau = This is one of the most important concepts of radiobiology.

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RBC have no nucleus, so they are not really effected.
There is 1 exception to his rule: White Blood Cells

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Radiation Weighting Factor

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Since different types of radiations have different RBE's, a weighting factor is used for purposes of radiation protection.

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Radiation Weighting Factor cont.

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Radiation dose multiplied by a weighting factor is called the equivalent dose and has a unit of Rems or Sieverts

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Radiation Weighting Factor cont. 3

Rems =

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Rad x quality factor

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Sieverts =

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Grays x quality factor

1 sievert = 100 Rems
100 Rems = 1 Sievert

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Quality Factors (Q) have no units

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Radiation Q
Alpha 20
High Energy Proton 10
Thermal Neutrons 2
Beta, Gamma, X 1

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Alpha particles are

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20 x more effective in damaging tissue then beta, gamma, x

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Using the above quality factors, 1 Rad of Alpha particles would have

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the same biological effectiveness as 20 Rads of 250 keV X-rays

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Occupational Dose Limits

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Personnel dosimetry is measured in fractions of Rem or Sieverts

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Occupational Dose Limits are specified by the Nuclear Regulatory Commission (NCR) and the

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NJ State Bureau of Radiological Health. Other states have similar departments of radiation control which normally specify exposure limits.

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Occupational Dose Limits

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Whole Body = 5 Rem/annum

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Any organ,skin and extremities

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50 Rem.annum

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Lens of the Eyes

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15 Rem/annum

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Why do you think there are different exposure limits for different parts of the body?

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???

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ALARA

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As Low As Reasonably Allowable

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ALARA Limits

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ALARA is the philosophy used by most radiation agencies.
- It is reasonable to lower occupational dose limits to 1/10th of the maximum allowed.

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ALARA Exposure Limits

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Whole Body 0.5 Rem/year or 500 mRem/year

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Any organ, skin, extremities

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5 Rem/year

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Lens of the Eyes

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1.5 Rem/year

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Radiosensitizers & Radioprotectors

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They are both only have a real effect with the indirectly ionizing radiations. They have little or no effect with high LET radiation.

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Radiosensitizers

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Are chemicals or pharmacological agents that increase the lethal effect of radiation when administered in conjunction with radiation.

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Any organ, skin, extremities

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5 Rem/year

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Radiosensitizers cont.

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Oxygen is the only radiosenitzers of any importance. Oxygen and other radiosensitizers, fix, or make permanent, the damage done by free radicals.

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Lens of the Eyes

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1.5 Rem/year

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Radiosensitizers & Radioprotectors

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They are both only have a real effect with the indirectly ionizing radiations. They have little or no effect with high LET radiation.

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Radiosensitizers

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Are chemicals or pharmacological agents that increase the lethal effect of radiation when administered in conjunction with radiation.

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Radiosensitizers cont.

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Oxygen is the only radiosenitzers of any importance. Oxygen and other radiosensitizers, fix, or make permanent, the damage done by free radicals.

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Any organ, skin, extremities

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5 Rem/year

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Lens of the Eyes

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1.5 Rem/year

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Radiosensitizers & Radioprotectors

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They are both only have a real effect with the indirectly ionizing radiations. They have little or no effect with high LET radiation.

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Radiosensitizers

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Are chemicals or pharmacological agents that increase the lethal effect of radiation when administered in conjunction with radiation.

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Radiosensitizers cont.

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Oxygen is the only radiosenitzers of any importance. Oxygen and other radiosensitizers, fix, or make permanent, the damage done by free radicals.

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Enhancement Ratio

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ratio of doses in the absence and in the presence of the drug that produce the same biological effect

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An enhancement ratio greater than 1 indicates a substance has a

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radiosensitizer qualities.

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Enhancement Ratio =

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Dose in rads to kill 63% of population w/o sensitizer/
Dose in rads to kill 63% with sensitizer

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Radio protectors

Dose Reduction factor:

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The ratio of radiation doses required to produce the same biological effect in the absence and in the presence of the protector.

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Dose Reduction factor =

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Dose to kill 63% of populations with radioprotector /
dose to kill 63% w/o the radioprotector

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A DRF greater then 1 indicates

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a substance has radioprotective qualities

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Radioprotectors work by
- Photons in your body make free-radicals

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scavenging the free radicals produced by the indirectly ionizing radiations, binding them before they can attack critical sites within the tissue or cell.
The most effective radioprotectors are sulfhydrl compounds.

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One such radioprotector is cysteamine which has the structure

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SH-CH2-CH2-NH2
Radioprotectors = not really effective, we don't really have any good radioprotectors.

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The problem with radioprotectors is that a useful concentration in the human body may also be toxic.

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To date, a compound called amifostine is the most useful and has been used as a radioprotector in some radiotherapy studies with promising results. Amifostine has been shown to have a dose reduction factor of 2.7 for 30 day death.

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There is much misinformation of radioactivity spread

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about in the media and web

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The two following ads for Potassium Iodide mislead the reader by making them think that this drug will protect them from all radioactive material.

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Actually, all it does is saturate the thyroid gland, making it difficult for additional radioactive iodine to enter the thyroid gland and increase the risk of one type of cancer, thyroid cancer

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Radium Curves

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High blood pressure, cancer, goitre, stomach trouble, arthritis, neuritis, female trouble, rheumatism, kidney failure, constipation, excema, piles, and more

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Radium Curves

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High blood pressure, cancer, goitre, stomach trouble, arthritis, neuritis, female trouble, rheumatism, kidney failure, constipation, excema, piles, and more

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Radium cures, which reached their pinnacle of popularity in the U.S during the 1920's....

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promised to remedy these diseases, restore youthful vigor, and revitalize an ailing sex life.

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Radium Bath House

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Claremore, Oklahoma

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Radithor

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Was pre-mixed radium water manufactured in New Jersey by W.J A. Bailey during the 1920's. Bailey called it the "Cure for the Living Dead" meaning a cure for mental illness and retardation.

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One of Radithor's fans was Eben Beyers a steel tycoon in Pittsburg.

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Mr. Beyers drank 1400 bottles of Radithor and became seriously ill with radium poisoning that portions of his mouth and jaw were surgically removed before he died in 1931. He death noted on the front page of the New York TImes, marked the beginning of the end of radium water cures

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Radium Water Cures
- The Revigoraotor, a crock lined with radioactive ore, was used to produce radioactive water at home. One scientist estimates that water left in these crocks overnight was 5x as radioactive as the maximum recommended for well water today

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Radioactive Water, popular in the 1920's was consumed by doctors and patients alike. Radioactive water is said to have a tonic effect.