RTMR 284 Chapter 30 : Fundamental Principles of Radiobiology

The Law of Bergonie & Tribondeau 1906 French Scientists researching that Stem cells are MORE radiosensitive Younger tissues & organs are radiosensitive  Metabolic activity,  radiosensitivity  proliferation & growth rate,  radiosensitivity exceptions to the rule that rapidly dividing cells are more sensitive to ionizing radiation: 1. some rapidly growing tumors are insensitive to radiation 2. lymphocytes which divide only occasionally are among the most radiosensitive. don't know why.

Physical Factors Affecting Radiosensitivity LET - Linear Energy Transfer RBE - Relative Biologic Effectiveness Fractionation & Protraction

Linear Energy Transfer (LET) Amount of energy transferred to tissue per distance traveled in that tissue. LET effects the biological damage produced in tissue by ionizing radiation As the LET increases the biological response increases Diagnostic x-rays are in the 3.0 LET range Fast neutrons are in the 50 LET range Heavy nuclei are in the 1,000 LET range LET is the amount of energy transferred to tissue per distance traveled in that tissue. Since the amount of ionization and the tissue effects that result from that ionization , are related to the amount of energy absorbed by the patient, linear energy transfer affects the amount of biological damage produced in us by ionizing radiation.

LET Scenarios Slow-moving, highly charged particles have a high rate of LET produce more ionization in shorter distance Fast-moving, lower charged particles travel further and deposit less energy. They have a low LET & cause less damage

Relative Biologic Effectiveness (RBE) RBE measures the damage done to the tissue As LET increases, RBE increases The RBE for diagnostic x-rays is 1 The maximum RBE is ~3 When mice are irradiated with 250 kVp x-rays 650 rad is needed for death with fast neutrons, only 210 rad is needed.

Fractionation & Protraction Two ways to reduce patient exposure Fractionation: high dose, with breaks in-between doses Protraction: the dose is delivered continuously but at a lower dose rate until all of the dose is given.

Fractionation & Protraction Example Example - mouse irradiation: 600 rad given in 3 min (200 rad/min) lethal 600 rad given @ 200 rad/min in 12 fractions of 50 rad each separated by 24 hours non-lethal fractionation 600 rad given @ 1 rad/min continuously protraction

Biologic Factors Affecting Radiosensitivity Oxygen effect Age Sex Recovery Chemical Agents

Oxygen Effect When tissue is in the oxygenated state (aerobic) tissue is most sensitive (low LET) Low oxygen state (hypoxic) tissue is less sensitive No oxygen state (anoxic) tissue is the most resistant

Comments Tissue is more sensitive with oxygen present and LOW LET With high LET the oxygen being present makes no difference as high LET is so bad already Sometimes they combine the HBO (hyperbaric chamber) with radiation therapy to make the tissue more oxygenated

Biologic Factors: Age and Sex Humans are most sensitive to radiation before birth and as infants Least sensitive to radiation in adulthood Humans are more radiosensitive again in old age Women appear to be ~5% LESS radiosensitive than men born with all their eggs, however sperm reproduces

Recovery If tissue or organ receives a major radiation dose, it will atrophy. Some cells die and are removed as waste. Human cells recover from radiation damage in two ways: Repair Repopulation

Repair & Repopulation Repair repair mechanism is inherent in the biochemistry of the cell cells are capable of repair, if the dose doesn’t kill the cell Repopulation surviving cells repopulate what if surviving cells are damaged?

Chemical Agents Some chemicals modify how cells, tissues, & organs respond to radiation usually need to be present at irradiation Radiosensitizers enhance the effect of radiation make body more sensitive to radiation Radioprotectors decrease the effect of radiation make the body less sensitive to radiation No human application (protector is toxic) -some chemicals can modify how cells, tissues, and organs respond to radiation. for this to happen the chemical agents usually have to be present at the time of irradiation. -using the chemical agent after the exposure will not usually change the radiation response. radiosensitizers agents that enhance the effect of radiation are called sensitizing agents. ---if 90% of a cell culture is killed by 200 rad .. if the chemical agent is present then only 100 rad would be needed for the same result. -one example of this is vitamin k radioprotectors -radioprotective agents have not found human application because, they would have to be given in a toxic dose in order to be effective. --if 500 rad is needed to produce an effect, then with the chem present, 1000 rad would be needed to produce the same effect. -the protective agent would be worse than the radiation.

Radiation Dose-Response Relationships A dose-response relationship is a graphic relationship between levels of radiation dose & the result of that dose Linear Nonlinear threshold nonthreshold

Linear dose-response relationships

Dose-Response Relationships Threshold The line on the graph starts higher than 0 Everything below 0 is considered to have no observable response There is a threshold where no response is expected Nonthreshold Any dose, no matter what its size, is expected to produce a response 1.a. nonthreshold dose-response ... any dose, no matter what its size, is expected to produce a response. b. nonlinear, nonthreshold see p. 539 no threshold, varied shape 2.a. threshold.... the line on the graph starts at a higher level, greater than zero. everything below that starting point is considered to have no observable response. so there is a threshold where no reaction will occur 2 b. nonlinear threshold is a threshold, varied shape.

Diagnostic Radiology’s Dose-response Relationship Linear non-threshold is used Why? Cannot directly measure low-dose response, so extrapolate information Safest assumption to make (no threshold) Overestimate the risk , use it to establish protection guidelines Conservative approach