In This Lecture
Fundamental Principles of • Radiosensitivity Radiobiology • Law of Bergonie & Tribondeau • Physical factors effecting radiation response • Biological factors effecting radiation response • Dose-response relationships
Radiosensitivity Law of Bergonie & Tribondeau
• Some types of tissue respond more • Radiosensitivty of living tissues varies with quickly to lower does of radiation than maturation & metabolism; others 1. Stem cells are radiosensitive. More mature cells are more resistant • Dose response relationship 2. Younger tissues are more radiosensitive – Mathematical function/graph relating 3. Tissues with high metabolic activity are highly radiation dose to observed response radiosensitive 4. High proliferation and growth rate, high radiosensitivty
Radiosensitivity
• Response of tissue determined by amount of energy deposited per unit mass (dose in Gy) Physical Factors Effecting Radiosensitivty • Two identical doses may not produce identical Radiosensitivty responses due to other modifying factors – Linear energy transfer Physical Factors Biological Factors Linear energy transfer – Linear energy transfer – Oxygen Effect – Relative biological effectiveness – Relative biological effectiveness – Age – Fractionation & protraction – Fractionation & protraction – Recovery – Chemical Agents – Hormesis
1 Linear Energy Transfer Linear Energy Transfer
• Measure of the rate at which energy is • Expressed in units of keV of energy transferred from ionizing radiation to transferred per micron of tracklength in tissue. soft tissue (keV/μm) • Another way of expressing radiation • Ability of radiation to produce biological quality & determining the value of the response increases as LET of radiation increase tissue weighting factor (WT) increase
• WT accounts for relative radiosensitivty • LET of diagnostic X-rays ~3keV/μm of various tissues
Relative Biological Effectiveness Relative Biological Effectiveness
Dose of s tandard radiation to produce a given effect • Higher LET, higher ability to produce RBE = damage Dose of test radiation to produce a given effect
• Standard radiation, by convention, is X-radiation • Quantitatively described by relative in the 200- to 250-kVp range biological effectiveness (RBE) • For diagnostic X-rays, RBE = 1
LET & RBE Example: Type of Radiation LET RBE
25-MV x-rays 0.2 0.8 When rats are irradiated with 250 kV
60Co X-rays 0.2 0.9 x-rays, 15 Gy is necessary to produce RBE 1-MeV electrons 0.3 0.9 death. If similar rats are irradiated Diagnostic X-rays 3.0 1.0 with heavy nuclei, only 0.5 Gy is 10-MeV protons 4.0 5.0 needed. Fast Neutrons 50.0 10 LET 5-MeV alpha particles 100.0 20 What is the RBE of the heavy nuclei ?
2 Fractionation & Protraction Fractionation
• A dose is delivered over a long period of • Divide dose into series of small doses time is less effective than that delivered • Example: quickly. If the 12 Gy dose is delivered at the same dose rate (4Gy/min), but in 12 equal fractions of 1 Gy • If the time of irradiation is lengthened, rate (4Gy/min), but in 12 equal fractions of 1 Gy • each separated by 24 hours, the rat will survive. higher dose is required to produce the The dose is said to be fractionated same effect. • Dose fractionation causes less effect due to • Lengthening of time accomplished in two intracellular repair & recovery between doses. ways; • Routinely used in oncology
Protraction
•Reduced Dose Rate Biological Factors Effecting •If the dose is delivered continuously but at a Radiosensitivty lower dose rate, it is said to be protracted. – Oxygen Effect – •Example: – Age – Recovery A total of 12 Gy is delivered in 3mins (4Gy/min) is – Chemical Agents lethal for a rat. However, when 12 Gy is delivered lethal for a rat. However, when 12 Gy is delivered – Hormesis at a rate of 1 Gy/hour for a total of 12 hours the rat survives.
Oxygen Effect Example • Tissue is more sensitive when irradiated in oxygenated or aerobic state than in anoxic or • When mouse mammary carcinomas are hypoxic state clamped and irradiated under hypoxic conditions, the tumor control dose is • Oxygen Enhancement Ratio (OER) 106 Gy. When not clamped the control dose is 40.5 Gy Dose under anoxic conditions to produce a given effect OER = Dose under aerobic conditions to produce the same effect • Calculate the OER
• Diagnostic x-rays are administered under conditions of full oxygenation
3 Age Recovery • Age of biological structure affects radiosensitivity • Cells are capable of recovering from • Humans are most sensitive radiation damage at birth • Sensitivity decreases until • At whole body level, recovery is maturity assisted via repopulation by surviving • In old age, radiosensitivity cells
increases Radiation Sensitivity to Recovery = Repair + Repopulation • Many theories have been developed to explain this. – In utero Birth ChildAdult OAP None universally accepted
Chemical Agents Chemical Agents Radiosensitizers • Radiosensitivty of cells, tissues, and • Examples: organs can be modified by chemical – Halgenated pyrimidines – Methotrexate agents – Actinomycin D – Hydroxyurea – Vitamin K • Must be present during irradiation • All have effectiveness of ~2
• If 90% of cell culture is killed by a 2 Gy dose, then in the presents of sensitising agent only 1 GY is required
Chemical Agents Hormesis
Radioprotectors • Evidence that a small dose of radiation • Examples: produces helpful effect – Sulphydryl groups – Cysteine and Cysteamine • Prevailing Explanation • Not found applications in humans Stimulation of hormonal and immune responses to other toxic environmental • To be effective, must be administer in toxic agents levels (can be worse than effects of radiation)
4 Dose-Response Relationships Linear Dose-Response • Mathematical relationship between radiation dose & magnitude of observed • Response directly radiation dose & magnitude of observed proportional to dose response
• Two important implications • Radiation-induced cancer & genetic 1. Planning therapeutic treatment effects follow a R 2. Provide information on low dose irradiation N 2. linear, non-threshold relationship • Two characteristics: Either linear or nonlinear DT DT
Constructing Dose-Response Nonlinear Dose-Response Relationships
• Radiation death •Nearly impossible and skin effects to measure low of high dose dose, late effects fluoroscopy •Limited number of Extrapolation
follow sigmoid- subjects Response type response •Resort to irradiating small
DT number of animals Dose with high dose
Summary
• Radiosensitivity • Law of Bergonie & Tribondeau • Physical factors effecting radiation response • Biological factors effecting radiation response • Dose-response relationships
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