INTERNAL RADIATION DOSIMETRY Health Physics Society 1994 Summer School Edited by Otto G. Raabe Vu cog Medical Physics Publishing Madison, Wisconsin‘Copyright 1994 by the Health Physics Society All rights reserved. No part ofthis publication may be reproduced ‘or distributed in any form or by any means without written permission from the publisher. ISBN 0.944838-47.2 “Library of Congress Catalog Card Number: 94-76682 Medical Physics Publishing 732N. Midvale Boulevard Madison, WI 53705 (608) 262-4021 Information in this book is for instructional use only. The editor, authors and. publisher take no responsibility for any damage or harm incurred as a result of use of this information, Printed in dhe United States of America. am KOZPONTY FAY WETATO TETETEOAYYTARA p> tettarva vive PR.AAG az. ant. 4 | Budapest, 18. 34. PREFACE ‘This text on Internal Radiation Dosimetry was written for student use in the 1994 Health Physics Summer School, which convened June 20-24, 1994, on the campus of the University of California, Davis, under the sponsorship of the Health Physics Society. The Health Physics Socicty is an organization of scientists and radiation protection specialists whose purpose is to protect mankind and the environmeat from the possible harmful effects of radiation while working to provide for the development and use of nuclear technology for the benefit of modem society. The summer school, which addresses different technical aspects of health physics each year, is held during the week preceding the annual meeting, ‘of the Society at a nearby location. As this book goes to press, we are also looking forward to the 39th Annual Meeting of the Health Physics Society in San Francisco, California, June 26-30, 1994. ‘The last summer school covering Internal Radiation Dosimetry was the 1983 Health Physics Summer School held at the University of Maryland, Baltimore, MD, July 12-17, 1983. Mauch of the inspiration for the 1994 Summer School and this book can be traced to the 1983 school which was ably planned and directed by Dr. Allen Brodsky as Academic Director and Dr. Jack Schubert as Dean. Many of the instructors in those 1983 classes are also instructors at the 1994 Summer School and contribators to this text. In the intervening, cleven years many changes and advances have been made in the science, methods, and practice of internal radiation dosimetry. For example, there is a new ICRP lung model, improved and more complete dosimetric methods, and a newly revised 10 CFR 20 as part of the Federal laws, These new developments are reflected in the pages of this text ‘The thirty chapters in this book were written by the instructors forthe 1994 Health Physics Summer School. All of the instructors are internationally recognized experts in their topic areas. Many of the instructors are American Board of Health Physics Certified Health Physicists (CHP) and are Diplomates of the American Academy of Health Physics. The contributors to this text and their affiliations are listed inthe "Contributors" section. Besides Lup to date information, they have provided in-depth perspectives drawing on active professional experience and practical understanding of the issues as well as the science ‘sociated with their topics. Because the various chapters were prepared by different ‘authors, some of the nomenclature may vary among the chapters. The reader should be ‘aware that the variables and symbols used in any given chapter may in some cases be ‘encountered in other chapters with different designations. On the other hand, the many standard symbols and terms encountered throughout tke book provide a continuity that is inherent in the various aspects of the subject matter. Slunits are used throughout. Also, the chapters are not random contributions, but a carefully assembled tour of the various aspectsof this fascinating and involved subject area. The first few chapters are for those new to the field, but the practicing professional will soon find a depth of sophisticated detail as the ‘various key topics are being developed. Even the expert should find useful advanced details and in-depth information conceming the newest areas of interest and progress in the field ‘As Dean of the school and organizer of the academic plan, I wish to acknowledge the support and confidence of the Health Physies Society Summer School Committee headed by Kenneth W. Price, the Health Physics Society Board of Director and President, Kenneth L. Mossman, and the Northern California Chapter. I thank them for trusting me with this responsibilty. I also thank the dedicated instructors and contributors who generously provided valuable advice, especially Ronald L. Kathren. The membors of the local 1994 ‘Summer Schoo! Committee at Davis provided the important operational planning and dedicated efforts that made this text and summer school a reality. Victor E. Anderson served as administrative Dean and provided skillful management of the business and financial aspects of the Summer School. The other members of the local committee included Don D. Honey, Henry Kocol, Gerry Westcott, Stephen V. Teague, and Mark T. Dirksen. Both the Northern California Chapter and the Sierra Nevada Chapter of the Health Physics Society ‘were represented in this effort. Special recognition and thanks go to Chengxian Gao who assembled and managed the computer files of the manuscripts and inserted the computer araphie images. It is our hope that this volume serves well the dual purposes of providing the reference ‘materials needed by the students enrolled in the 1994 Health Physics Summer School and providing a useful text and reference book for others who may be interested in leaming about the fascinating seieutific aud technical components of Intemal Radiation Dosimetry Otto G. Raabe, Ph. D., CHP Dean, 1994 Health Physics Summer School Professor University of California Davis, California 95616 15 April 1994 CONTRIBUTORS (Carol D. Berger, CHP IT Corporation Washington DC 20036 Liz Bertelli, Ph.D. National Nuclear Energy Commission Rio de Janeiro, RJ, Brazil Wesley E. Boch, Ph.D., PE, CHP Texas A & M University College Station, TX 77843 Jerrold T. Bushberg, Ph.D. University of California, Davis, Medical Center Sacramento, CA 95817 Eugene H. Carbaugh, CHP Battelle Pacific Northwest Laboratories Richland, WA 99352 ‘Herm Cember, Ph.D., CHP Northwestern University Evanston, IL 60208 George E. Chabot, Ph.D, CHP. University of Lowell Lowell, MA 01854 Mark Cristy, PLD. ak Ridge National Laboratory ak Ridge, TN 37831 Keith F. Eckerman, Ph.D. (Oak Ridge National Laboratory: ‘Oak Ridge, TN 37831 Danell R. Fisher, Ph.D. Battelle Pacific Northwest Laboratories Richland, WA 99352 Clayton 8. French, Ph.D., CHP. University of Lowell Lowoll, MA 01884 Samuel E, Glover, MS. University of Cincinnati Cincinnati, OH 45242 David P. Hickman, Ph.D. __Lawrence Livermore National Laboratory Livermore, CA 94551 Anthony C. James, PLD. Battelle Pacific Northwest Laboratories Richland, WA 99352 Ronald L. Kathren, D.E.E., CHP ‘Washington State University Richland, WA 99352 ‘Thomas R. La Bone, MS. Westinghouse Savannah River Site ‘Aiken, SC 29808William A. Mills, Ph.D. Oak Ridge Associated Universities Washington, DC 20036 John W. Poston, Sr, Ph.D. Texas A & M University College Station, TX 77843 Otto G. Raabe, Ph.D., CHP University of California, Davis, CA 95616 Narayani P. Singh, Ph.D. University of Utah School of Medicine Salt Lake City, UT 84112 Kenneth W. Slanble, Ph.D., CHP University of Lowell Lowell, MA 01854 Monts B. Snipes, Ph.D. Inhalation Toxicology Research Institute Albuquerque, NM 87185 Hemy B. Spitz, PhD. University of Cincinnati Cincinnati, OH 45242 Michael G. Stabin, CHP Oak Ridge Institute for Science and Education Oak Ridge, TN 37831 Paul S. Stansbury, Ph.D. Battelle Pacific Northwest Laboratories Richland, WA 99352 Daniel 4 Strom, Ph.D, CHP Battelle Pacific Northwest Laboratories Richland, WA 99352 Richard E. Toohey, Ph.D., CHP Washington State University Richland, WA 99352 Evelyn E. Watson, BA. ak Ridge Institute for Science and Education (ak Ridge, TN 37831 George L. Voelz. M.D. Los Alamos National Laboratory Los Alamos, NM 87545 ‘McDonald E. Wrenn, Ph.D., CHP University of Utah School of Medicine Salt Lake City, UT 84112 Table of Contents Preface List of Contributors ‘Table of Contents Chapter 1: Introduction to Intemal Radiation Dosimetry Otto G. Raabe Chapter 2: Physical and Chemical Interactions of Radiation with Living Tissues Wesley E. Bolch Chapter 3: The Biological Basis for Radiation Dosimetry Herman Cember Chapter 4: From "Micro" to "Macro" Intemal Dosimetry Darrell R. Fisher Chapter S: An Overview of Monte Carlo Techniques Used in Infernal Dose. Calculations and Their Statstital Interpretation Paul S. Stansbury Chapser 6: The Internal Radiation Dosimetry Aspects of the New 10CFR20 Regulations. John W. Poston, Sr. Chapter 7: Charncterization of Radioactive Airborne Panicles Otto G. Raabe Chapter 8: Dosimetric Applications of the New ICRP Lang Model ‘Anthony C. James Chapter 9: Dosimetry of Inhaled Radon and Thoron Prozeny Anthony C. James Py a 6 9s m1 143 1stChapter 10: (Chapter 11: (Chapter 12: (Chapter 13: Chapter 14: Chapter 15: Chapter 16: (Chapter 20: Chapter 21: Biokinctics of Inhaled Radionuclides Morris B. Snipes Biokinetics of Bone-reeking Radionuclides Richard E. Toohey Reference Man Anatomical Model Mark Cristy Dosimettic Methodology of the ICRP Keith F. Eckerman Use of Multi-compartment Models of Retention for Intemally Deposited Radionuclides Kenneth W. Skrable, George E. Chabot, Clayton S. French and ‘Thomas R. La Bone ‘The MIRD Intemal Dose Methodology Evelyn E. Watson Patient Dose from Diagnostic and Therapeutic Radiophammaceaticals Michael G. Stabin In Vivo Measurements David P, Hickman ‘Analytical Measurements for In Vitro Bioassay of Radionuclides .. ‘Narayani P, Singh Estimation of Intakes from Repetitive Bioassay Messurements Kenneth W. Skrable, George E. Chabot, Clayton S. French and ‘Thomas R. La Bone Evaluati Therpy Thomas R. La Bone of Intakes of Transuranics Influenced by Chelation Evaluation of Historical Plutonium Urinalysis Data Henry B. Spitz and Samuel E. Glover ts 197 27 239 227 355 375 393 409 461 a7 Chapter 22: (Chapter 23: Chapter 24: Chapter 28: Chapter 26: Chapter 27: Chapter 28: Chapter 29: Chapter 30: Appendix: Index Dose Reconstruction from Bioassay Measurements of Long-Lived Residual Activity MeDonald E, Wrenn and Luiz Bertelli Postmortem Verification of Internal Dose Ronald L. Kathren Practical Applications of Intemal Dose Calculations Eugene H. Carbaugh Programs for Assessment of Doses from Intakes of Radioactive Materials Daniel J. Strom Quality Assurance in Intemal Radiation Dosimetry Programs Carol D. Berger “The Perfect Intemal Dosimetry Code ‘Thomas R. La Bone Medical Management of Intemal Contamination Accidents George L. Voelz and Jerrold T. Bushberg, Estimates of Human Cancer Risks Associated with Intemally Deposited Radionuclides William A. Mills ‘Taree-dimeasional Models of Risk from Internally Deposited Radionuclides Otto G. Raabe ‘Summary of Units and Conversion Factors 495 317 329 343 sm 385 595 609 633 657 661Chapter 1 INTRODUCTION TO INTERNAL RADIATION DOSIMETRY (Otto G. Raabe eS OVERVIEW Internal radiation dosimetry is the scientific methodology used to measure, calculate, estimate, assay, predict, and otherwise quantify the radiative energy absorbed by the ionization and excitation of atoms in human tissues as a result of the emission of energetic radiation by internally deposited radionuclides. In this context the word intemal refers to ‘the source of the ionizing radiation as being within the human body. The physical quantity of radiative energy transferred to a specified mass of tissue is called the radiation absorbed dose. The timing of delivery of this absorbed energy is important in establishing the dose rate and for accounting for temporal changes in the pattem of irradiation caused by radioactive decay, metabolic processes, and new intakes of redionuclides. The chemical properties of a radionuclide and of its decay products affect the biokinetics and associated temporal variations. The type of ionizing radiation emitted affects the intensity, range, and fractional absorption in the tissue or organ. The radioactive decay products ané their distinctive behaviors provide additional sources of radiative energy. The assessment and evaluation ofthe risks or effects associated with internally deposited radionuclides must be based upon appropriate and accurate internal radiation dosimetry. This chapter reviews the basic concepts involved in intemal radiation dosimetry, the terminology and dimensional units used for dose measurements, and the general factors that need to be considered RADIOACTIVITY A nuclide is a species of atom having a specified number of nevtrons and protons in its nucleus, The general symbol for a nuclide is given by 4X where Z is the atomic mumber of protons in the nucleus, A is the atomic mass mumber of total nucleons (neutrots plus ‘protons), and X is the symbol of the clement represented by the nuclide. The number of nuclear neutrons in an atom is given by A-Z. The actual mass of atoms and nuclear particles is measured in atomic mass units (u) where the mass of the electrically neutral carkon-12 (7C) atom is defined as exactly equal to 12 atomic mass units. Certain nuclides have nuclear structures that are 100 big, have too many neutrons, toc many protons, or are otherwise unstable. This instability is founded in the fact that a slightly altered state has a lower total energy. These unstable nuclei spontaneously undergo nuclear2 Raabe ‘transformations with the release of the excess energy in the form of ionizing radiation Energy of decay is typically expressed in very small energy units known as electron volts (@¥), defined as the kinetic energy acquired by an electron as it traverses a potential difference of one volt in a vacuum. The process of spontaneous nuclear transformation with sccompanying energetic emission is refered to as radionuclide decay, nuclear disintegration or transformation, andlor radioactivity. The energy released involves the conversion of a small fraction of the nuclear mass following Einstein's famous equation of mass-energy equivalence: E = me” = 931.5 MeViu. The speed of the radioactive decey process depends uniquely on the overall stability of a given nuclide. The decay is a random process so that it is not possible to predict when a specific radioactive atom will decay However, the instantaneous fraction ofa large number of radioactive atoms in a sample that decay per unit of time san be deseribed by the decay constant (8). Likewise, the physical halflife (Ty,), defined as the time required for one-half of the radiosctive stoms in a sample to decay, can be obtained from the decay constant by 1, Pye ‘The physical half-life and decay constant arc fixed characteristics of each radionuclide Half-lives may range from a fraction of a second to billions of years. The number of radioactive atoms, n, remaining after a period of time, t, is described by an exponential decay process: (nD /4 = 0.693/. aay n@) = ne where m, is the initial xumber of radioactive atoms, Each radionuclide has characteristic physical half-life, decay constant, emission pattem or type, and energy of Aecay and radiation, which values can be found in nuclear reference books or charts of the nuclides (ICRP, 1983; Lederer & Shirley, 1978; General Electric, 1972), ‘An analogous term isthe biological retention half-time (Ty), which is defined as the time required for one-half of a given quantity of a radionuclide to be cleared from the body or from a specified organ of the body via physiological and biokinetic processes. The biological half-life is dependent upon the chemical form of the radionuclide, route of entry into the body and various metabolic processes. The combination of the physical and biological halves acting together result in an effective retention half-time (Ty,) which is related to Ty and Ty, a8 follows: gz a3) z i, a Toe Tp If cither Ty, or Ty, differ substantially, the smaller will control the retention of the radionuclide in the body tissues. Introduction to Internal Radiation Dosimetry 3 ‘The radionuclide undergoing decay is referred to as the parent nuclide and the transformed nuclide is called the daughter or decay product. The daughter may be no more stable than its parent and may also be radioactive. Successive transformations will occur in a so-called decay chain, possibly yielding soveral radioactive progeny, until a stable nuclide is reached. ‘There are many naturally occurring radioactive nuclides that are continually being produced from decay chains in which the parent has a very long physical half life. For example, radium-226 (Ra) is present in all the soil and rock on the earth as a product of the decay series headed by uranium-238 (™"U) whose half life is comparable to the age of the earth (43 billion years). The ™"U decay series is shown in Figure 1-1, bh mp ng are PT RU de Be a a are 8s 6 ROT 34 Osos 2 nH 198mn nw Ltn Ete LE ag Poem PD Bl eaPOTT ET ag PP (stable) Figure 1-1. Schematic illustration of the natural "U decay series as found in all the soil and rock on the surface of the planet Earth ‘Tae quantity of radioactive material expressed as the number of radioactive atoms ‘undergoing nuclear transformation per unit time, is called the activity, The Systeme ‘Intemational (SI) unit for activity is the Becguerel (Bq), named for Henri Becquerel who discovered radioactivity in 1896, The becquerel is defined as one disintegration per second (ps). The activity can be calculated from the number of radioactive atoms of a specified ‘ype in a sample using the decay constant by. a = Ang) 4) where n(t) is the number of radioactive stoms present and a(t) is the activity at time t GECRP, 1985; Evans, 1955).4 Rasbe Introduction to Internal Radiation Dosimetry 3 IONIZING RADIATION ‘The iotizing radiation emitted by internally deposited radionuclides may be in the form of ‘energetic subatomic particles or electromagnetic radiation. Transfer of energy from these radiations to orbital electrons may result in the removal of one or more orbital lectrons ‘rom neutral atoms changing them to charged ions. Ionization is the first step in acomplex tories of reactions within living tissue that may lead to biological alterations or cellular damage, In this context, intemal radiation dosimetry does not consider other forms of radiation that are not ionizing such as infrared radiation, ultraviolet radiation, microwaves, clectrical fields, and magnetic fields. These forms of non-ionizing radiation may also cause biological effects of course. The principal forms of ionizing radiation of interest for internal radiation dosimetry are listed in Table 1-1. The interactions of radiation with tissues or other physical matter are summarized in Table 1-2 (Chase and Rabinowitz, 1962), Energetic Subatomic Particles Energetic subatomic particles of matter can directly or indirectly cause the ionization of atoms by virtue of their kinetic energy of motion, Important forms of energetic subatomic particles include alpha particles (a), beta particles (), and positrons (f°) thet originate from the nuclei of atoms during radioactive decay, noutrons (n°) that are produced in nuclear fission, and electron radiation (e") that originates from extranuclear orbital electrons (Evans, 1962) Alpha particles. Alpha particles (2) consist of a bundle of two protons and two neutrons equivalent to a helium-4 (‘He) atomic nucleus without orbital electrons. At 4.002 u, they are about 7500 times as massive as an electron. Alpha particles are typically emitted from the nuclei of larger unstable atoms having high atomic number of protons (Z) and high total umber of nucleons (A). Alphas are emitted with high kinetic energies usually from 3 10 9 MeV. However their range is limited to a few om in air and < 100 ym in tissue, Since alpha particles cannot penetrate the Keratized surface or "dead" layer of human shin, alpha particle irradiation is only biologically important for internally-deposited alpha-emiting radionuclides. In radioactive decay, alphas are emitted at fixed, discrete energies (in the range of 3-9 MeV) which are characteristic of a given decay scheme, Alpha decay can be ‘soneralized in the following way: 2K + TRY + fo? + Boergy sy Example: WRa ~ (Rn + ja + 4.87 MeV (14) For example, the primary alpha particles emitted by ™*Re display 2 kinetic energy of 4.78 MeV. The recoiling, atomic nucleus carries a small portion of the available energy of the docay. In this case the decay product is ™*Rn having a recoil energy of 0.09 MeV. Frequently, there are also lesser energy alpha particles emitted at much lower probabilities along with low energy gamma rays. Table 1-1. Summary of some properties of ionizing radiations. ‘Approximate | Approximate range | Primary Radiation | Charge | energy range [— vas] wee Energetic particles ‘Alpha [42 31 9MeV [28cm | 20umt0 | Some nuclei of 100 ym | high Z Electron ‘Nocti with Gea ow 3Mev | upto [Upto —_ | high (bets) or @ositron) Rm afew mm | low (positron) fp" ratio Newton | 0 00 10Mev | Upto | Uptotm | Nuclear 100 m reactions Blectromagietic rays Orbital xray [None | AfeweVto | Afewmm | Upto | electron several MeV | t010m | afew em | transitions and Bremsstrahlung Gamma rorevio | Atewem | roma — | Nuclear ny None | 10MeV | t0 100m | few mm to | transitions several em Beta particles and positrons. Beta particles tend to be emitted by nuclides with excessively ‘high nuclear neutron/proton ratios. Conversely, positrons tend to be emitted by nuclides with low nuclear neutron/proton ratios. Beta particles and positrons are simply electrons (0.00055 u, negatively and positively charged, respectively) that are emitted from an atomic nucleus during radioactive decay. These electrons can travel several meters in air and can penetrate several cm in tissue, depending on their energy.6 Ranbe In beta decay an energetic electron and a neutrino (v) are emitted from the nucleus producing a daughter nuclide with one less neutron and one more proton. This is the conversion of a nuclear neutron to proton with the emission of the beta particle. The neutrino is an uncharged subnuclear particle having negligible mass that carries away a portion of the kinetic energy’ associated with the beta decay but does not contribute to tissue dose because of its very low probability for interaction. Unlike alpha decay, the kinetic ‘energy of beta particles spans from zero to a maximum which is characteristic of pasticularradionuclide's decay scheme. Typically, the average kinetic energy of the f° and the neutrino is 1/3 and 2/3, respectively, of the total avsilable energy (Eqy,)- The result is ‘a nuclide with the same mass number, A, but with atomic number Z, increased by 1. Beta decay can be described as: 4x 4,.¥ + po + v + nergy a Example: Bp 8s + p+ v + 1.71 MeV a8) In this case, the B* particles will be emitted with a spectrum of energies ranging from zero to a maximum (Eq,,) of 1.71 MeV with an average energy (E) of about 0.57 MeV. Positron (B") decay involves the conversion of a nuclear proton to a neutron so that the ‘atomic mass number A is unchanged but the atomic number Z, decreases by one. The decay involves the emission of @ positron and an antineutrino (6). The (particles are emitted ‘with a spectrum of energies from 7210 10 Fay and an average energy equal to about VB Ex, in a manner that is analogous to beta decay. However, the fate of the positron is completely diferent from that ofthe beta since its combination with an available ordinary clectron results in mutual annihilation and the emission of two 0:51 photons of clectromagnetic annihilation radiation. Positron decay can be described as: 4x fy + pr + 6 + Boergy ( 9) Example: Mp = Ho + B° + 6 + 0.635 MeV (Kinetic energy) (1-10) which will be followed by the emission of an additional 1.02 MeV of annihilation radiation at the location where the positron combines and is annihilated along with an electron Energetic electrons. Electron capture decay occurs when the nucleus captures an orbital clectron. The net result of this process is similar to, and in fact competes with, positron decay by producing a daughter nuclide with one additional neutron and one less proton. Energy is emitted as monoenergetic neutrino and results in an excited product atom. Electron capture decay can be generalized in the following way _ Sir Introduction to Internal Radiation Dosimetry 1 WK + eo> RAY" +0 + nergy aay with the excited decay product indicated by the asterisk Examp! ra - Rn" + » + 053MeV oan 12) Wn’ - PRh + le” + 23keV In this example the 17.5 day halflife “Pd captures a K shell electron converting it to 37 min half-life energetic "’Rh* which decays either by gamma emission or the energy is iransferred by process called internal conversion to another orbital electron that is energetically ejected from the atom. The vacancy left by the ejection of this electron is filled by an electron transition from an outer shell and its vacancy is filled by another clectron of lower binding energy. This process repeats nil the atom establishes electronic neutrality. Following K shell electron capture and the fling of the vacancy, the excess nergy of this transition is emitted either as an x ray (called a characteristic x ray) or the ection ofa lower energy electron (called an Auger electron). Auger electron emissions are favored for atoms with alomie numbers less than 30. "Neutrons. Neutrons (n°) can be produced by the decay of some heavy unstable (radioactive) lements such as califomium-252 (**Cf) that can fission spontaneously. At 1.009 u, ‘eatrons are about 1800 times the mass of an gJectron and have no net charge. A one MeV neutron has an average depth of penetration of 2.5 em in tissue, Interaction with tissues. Charged particles interact with mater and lose their kinetic energy via excitation, ionization and/or radiative losses (Table 1-2). Excitation occurs when the clectrostatic Coulomb-force field of a charged particle approaches close enough to an atom's ‘ofbital electrons to allow the transfer of some of the particle's kinetic energy either by attraction (as for positively charged alpha particles, protons, or positrons) or by electrostatic repulsion (as for beta particles). This transfer of energy may cause one or more orbital electrons to be temporarily promoted to high energy states, a process called excitation. If the transferred energy exceeds the binding energy of the orbital electron, the orbital electron is removed from its parent atom and an ion pair is created in the process called fonization. In come cases the removed electrons receive enough kinetic energy tn ionize other atoms in a process called secondary tonization. These secondary electrons, called delta rays, follow separate, short ionization paths,‘Table 1-2. Summary of interactions of ionizing radiations with matter (main processes in bold. pects ease pete ce mance comet shorn Fee Een Eee] eee are Orbital (Negligible) | Ionization and =| None aS on SS GSS See a a a ete =e Bete | et [cemrsone | Steaaee | Arann acest o hemes ea | cana | roar = Besta [Reams | Sando vena | aesoaee |oomcng | Soames Nemes = oi cama | exist | Oeaionin | Nee = res) ions eee vs |e Pattern Fare Pit aaa onc ce # ‘scattering ‘Compton effect | and internal Some Fal =| pars omen P| ra ema a A beta particle or energetic electron may emit some electromagnetic radiation if it traverses ‘an atom chse enough to have its path deflected by the strong fleld of the positive clectrostaic charge ofthe nucleus. During this deflection there is a reduction in its kinetic energy which is emitted as electromagnetic radiation (x ray). This process is called ry Introduction to Internal Radiation Dosimetry 9 bremsstrahlung, German word meaning "braking radiation". Bremssirahlung is primarily important for materials with high atomic number, s0 that most body tissues which are mostly water, yield litle measurable bremsstrahlung radiation. An important exception is tte skeleton; beta-emiting "Sr¥°Y deposied inthe skeleton yields bremsstrahlung radiation that can be measured outside the body. Since a neutron is electrically neutral, it interacts with matter by transfer of kinetic energy during collisions with atomic nuclei resulting in nuclear recoil and slowing (moderation) of the neutrons. The recoil of hydrogen nuclei present in the body results in the positively charged protons acting as ionizing radiation in a manner similar to alpha particles. Electromagnetic Radiation Electromagnetic radiation involves oscillating electric and magnetic fields perpendicular to ceach other and their direction of propagation (Figure 1-2). When emitted from a radioactive ‘tom, electromagnetic radiation radiates away in a specific but randomly selected direction at the speed of light, ¢ (310° m/s in a vacuum). The frequency (v), the number of waves, that pass a given point per unit time, is a function of the energy astociated with the electromagnetic emission. The wavelength (2,) of electromagnetic radiation oscillations is the distance between two adjacent waves. Frequency and wavelength are inversely proportional to each other and are expressed in units of cycles per second or Hertz (Hz) and meters, respectively, such that v 2,= ¢ Figure 1-2, Schematic illustration of the electric field (E) and magnetic field (H) oscillations associated with electromagnetic radiations. Both the electric field and magnetic ficld waves are perpendicular 10 the direction of propagation at the speed of light, ¢. The ‘wavelength is shown ah, Electromagnetic radiation extends from the very low frequencies associated with electric power transmission (60 Hz) to cosmic radiation (~ 10% Hz) in a continuous electromagnetic10 Raabe Yt Introduction to Internal Radiation Dosimetry un spectrum (Figure 1-3). It includes, in order of increasing energy or frequency and decreasing wavelength, radio and TV broadcasts, microwaves, visible light, x rays and gamma rays Gamma rays (j) ar the name given specifically to electromagnetic radiation emitted from the nucleus of a radionuclide; x rays refer tothe ionizing electromagnetic radiation emitted by energy transitions of orbital electrons or bremsstrahlung. The characteristics of radiation interaction with matter change dramatically at a function of energy (frequency). High ‘nergy electromagnetic radiation often exhibits a corpuscular behavior in is interaction with matter so that it can be treated as consisting of small bundles of energy called photons (energy Eye, = hy where hs Planck's constant). Only electromagnetic radiation with energies above those associated with ultraviolet rays are forms of ionizing radiation, Wotemte(e) 8 ttt Frown “82 oe we a ‘roaieast = ‘Shortwave — Gamma rays we ‘|| = —_. Pome, a Kore = a Toomer fg a Figure 1-3. Schematic representation of the various types of radiations associated with the electromagnetic spectrum showing the relationship of the wavelength (m), the frequency. (Hz) and the photon energy (€V). Only the radiation with energies above the ultraviolet (UV) range are forms of ionizing radiation Gamma rays are frequently emitted along with and virtually simultaneously with energetic particles during radioactive decay of radionuclides. During other types of radioactive decay 1 daughter is often formed in an excited (ie., excess energy) stale, Gamma rays are emitted as the daughter nucleus undergoes an internal rearrangement and changes from the excited state toa lower energy state. This provecs is refered to as isomeric transition, Once created, most excited states instantaneously convert to a lower energy state with the simultaneous ‘emission of a gamma ray. In some cases the excited state persists with half-lives that range from sbout 10° seconds to more than 100 years. These excited states are called metastable ff isomeric states and are denoted by the suffix m afer the atomic mass number (¢.. rte), Decay by isomeric transition can be generalized in the following way: 4x - 4 + y andor e° + Boergy (1413) Example: Bite ~ Ble + y andjor e~ + 142 keV ata Technetium-99m (Tc) is the primary radionuclide used in diagnostic nvelear medicine due to its relatively short half-life (6,02 hr), suitable photon energies for external imaging with gamma ray cameras, and the relatively few particle emissions that would inerease the dose to tissues. Interaction with matter. High energy electromagnetic radiation interacts with matter in several ways. The most important types of interactions, in order of increasing probability as a function of photon energy, photoelectric effect, Compton effect or scattering, and pair production (Table 1-2) In photoelectric absorption the energy of the electromagnetic radiation is completely absorbed as itis transferred to an orbital electron (typically an inner K or L shell). This electron is subsequently ejected with a kinetic energy equal to the incident photon energy minus the binding energy of the ejected Alectron. Photoelectric effect is particularly important at lower electromagnetic radiation energies such as for lower energy x rays Compton effect is the predominate interaction with tissue of medium energy photons (100-1000 keV). In Compton effect, an incident photon interacts with an outer orbital clectron that is ejected from the atom while the resulting lower energy photon is scattered at an angle from the original direction of propagation. The kinetic energy of the ejected ‘Compton electron depends on the energy of the incident photon and tke angle of photon scattering. As the angle of the deflection is increased, the energy transfered to the electron increases. The ejected electron deposits its energy via excitation and ionization as the field of its electrostatic charge interacts with neighboring atoms. The scattered photon may ‘undergo subsequent Compton interactions and/or deposit the balance of its energy by photoelectric absorption ‘When very high energy photons (> 1.02 MeV) interact with high Z. atoms, pair production ‘may occur. Pair production refers to the instantaneous creation of a elestron-positron pair ‘san energetic photon is converted from energy to matter under the inluonce of the atomic nucleus. The 1.02 MeV threshold for this interaction is equivalent to the rest mass energy2 Ranbe Se Introduction to Internal Radiation Dos 13 ‘of the electron and positron. Energy in excess of the 1.02 MeV threshold needed to create ‘the mass of two electrons appears as the kinetic energy of motion of the electron and ‘positron, Both the electron and positron transfer energy by ionization and excitation of atoms. However, when the positron slows down it interacts violently with an available electron converting their combined masses to pure energy resulting in the emission of two oppositely directed 0.51 MeV photons. These photons, referred to as annthilation radiation, ‘will undergo subsequent Compton and photoelectric interactions. Photoclecric effect is most Jmportant for photor energies exceeding 2 MeV. “The interaction ofelsctromagnetic radiation with mater by these various random processes results in the atemuation of the radiation intnsty with distance traveled, The linear artenuation coaficient () is defined as the differential fraction of incident photons interacting with tissue or other matter per unit of path length (cm™) in an exponential process given by reg (1s) where the incident photon intensity (I, ) is reduced to T after traversing a distance x in tissue so that the fraction of the radiation interacting with tissue in the traversal is (I-IV, or 1-€™, For example, a jt, of 0.2 cm” for 80 keV photons in tissue will result in 1 = 0.18 or 18% reduction in radiation intensity in passage through one cm of tissue Hence, 18% of the energy of the radiation is absorbed or scattered by one om of tissue slong the path of the radiation. RADIATION DOSIMETRY Absorbed Dose ‘The transfer of eneray from the various forms of ionizing radiation to tissue may involve both dirct atomic ionization-excitation events and indirect forms of kinetic energy transfer 18 for neutrons and photons. The first stage of this process for neutrons and gamma photoas ‘can be identified by the quantity kerma, K, a measure of the kinetic energy released 0 ‘mater. This quantity is given by oes 1-16) xo (1-16) where dogs is the kinetic energy transferred to parcel of tissue of mass dim, The SI units of kerma are Jkg ot Gray (Gy). Ultimately, the energy transferred to and absorbed in the tissue by ionization and excitation of atoms contributes to an absorbed dose. The specific ‘energy imparied to x small parcel of tissue is given by: os aan ‘where 2 (Gy) is the specific energy and de is the energy absorbed by the tissue mass dm, The specific energy is clearly a stochastic (statistically random) quantity since different ‘mass units may absorb different doses over a selected period of observation depending on the size of the parcel, Figure 1-4 shows the statistical variation of multiple measurements of specific energy in a spherical tissue parcel containing a fairly uriform concentration of 4 radionuclide, When the diameter and mass of the tissue parcel increases, the mean absorbed dose D is observed with increasing better reproducibility Figure 1-4 Ilustration of the variation of the specific energy, 2, in a spherical mass of tissue of diameter d and mass m at the center of a large organ containing a uniformly ted radionuclide emitting jonizing radiation with fairly long range of ionization —interections The mean absorbed dose, D, is indicated by the solid and dashed Lincs. A practicable definition of the absorbed dose is given by’ ae & (1-18) where D (Gy) is the absorbed dose and d& is the mean energy imparted to tissue of mass: 44m. Itis a common practice in dosimetry to calculate the mean absorbed dose to the whole target organ or total mass of critical tissue for an internally deposited radionuclide ws:4 Raabe p= fomam where D is the mean absorbed tissue dose, Dm) refers to the absorbed dose to a small clement of tissue mast, dm, and m, is the total mass ofthe target organ or critical tissue. ‘The dose rae is given by’ rap) (1-19) C imes whore d (Gy/) is the instantaneous dose rate, and t isthe time variable, so that, over time: (1-20) ‘where d is the time-weighted average dose rate to the tissue and u is the time surrogate. Kerma incluées some energy deposited outside the selected target mass, but this may be compensated by energy deposited from losses from adjacent similar masses. Using the average kinetic energy transferred to the selected parcel of tissue for kerma and assuming the complete balance of lostes from adjacent parcels results in kerma being about equal the mean absorbed dose D. Figures 1-5, 1-6, and 1-7 illustrate the relationship of kerma, absorbed dose, and exposure, where exposure, X, is usually defined only for air as the ‘generated ionization charge per unit mass (Wyckoff, 1983) Figure 1-5. Schematic representation of an incident gamma photon interacting by Compton scattering at B/ Electron point A within a spherical mass, 1m, of tissue or specified material to produce an energetic electron with a track ABC and a scattered photon. ‘The contributions to exposure (X), Soattered ema (K), and absorbed dese (D) ae shown with Que the charge of ee sign aznrted ty inion fom the ene elem, ebe | yA x AC y inti nergy of he lots at A, m X= and exp the energy imparted to the ‘mass, m, by the electron. YF Introduction to Internal Radiation Dosimetry 1s Figure 1-6, Schematic representation of an incident neutron interacting at ‘point A within a spherical mass, 1m, of tissue or specified material to produce an energetic charged particle with a track ABC and a scattered neutron. The contributions to kerma (K), and absorbed dose (D) are shown with te the kinetic energy of the charged particle at A, and Ey the energy imparted to the mass, m, by the charged particle Figure 1-7, Schematic representation ‘ofan incident energetic charged particle interacting at @ point A ‘within a spherical mass, m, of tissue ‘or specified material to produce secondary energetic charged particles with tracks AC and AG. A tertiary charged particle is generated at E with track EF. The contributions to absorbed dose (D) are given by the quotients of the energies (@) imparted along the tracks AB, EF, and AG to the mass, m. ‘Charged Particle Incident Charged Particle Eng + Cer + Encry - Introduction to Internal Radi ion Quality Ionizing radiation of verious types displays different intensity and pattem of ionization reactions in body tissues, In particular, the specific ionization intensity per unit of path length has a marked effect onthe potential biological response, For this reason the absorbed dose that is calculated from one type of radiation cannot be arithmetically added to the ‘absorbed dose from other types of radiation, For example, the dose associated with recoil ‘muclei during alpha emissions is characterized by high intensity of ionization but very short range in tissues. The alpha particles’ longer ranges in tissue (usually about 30 to 70 um) ‘yield less intense ionization tracks than the recoil nuclei, but considerably more intense than the tracks associated with energetic electrons, beta particles, or gamma photons. These inherent differences in specific ionization intensity should be expected to yield differences in relative biological effectiveness (RBE) among the different types of ionizing radiation fa (24 where ¥ isthe radius ofthe sphere. ‘Both LET and lineal energy in water or tissue are useful in desing radiation quality, but the LET is a non-stochastic (non-random) quantity subject to energy cutoff while the lineal ‘nergy is a stochastic (statistically random) quantity subject to geometric constrains, ‘Typical values of LET are summarized in Table 1-3. ‘Table 1-3. Linear energy transfer (LET) and radiation quality weighting {factors (w,) for various types of radiation." depending upon the circumstances. Even without a clear understanding of these differences in RBE, the dosimetrist is obligated to clearly segregate doses of different radiation quality. “The linear energy transfer (LET) of ionizing radiation in matter is given by: 21) where dE is the energy lost in specified medium in traversing the very short distance dé due to those interactions with electrons in which the energy lost is less than 4. Energy transfers grester than tae energy cutoff A are assumed to create delta rays of sufficient cencrgy to establish an independent ionization track. For internal dosimetry it is common to describe the quality of ionizing radiation using the unrestricted LET = L, in livirg tissues ‘or water, The unrestricted LET is also called the linear collision stopping power The lineal energy, y, is defined by: y 2) where © is the energy imparted to matter in a volume of interest by an energy deposition covent and where VOLUME OF TARGET PROJECTED AREA OF TARGET (1-23) is the mean chord length in that volume, The mean chord length depends upon the shape of the volume, The mean chord length for a sphere is given by: ‘Type of Radiation LET Radiation Weighting (keVipm) Factor wy (SviGy) xrays 02-2 1 ‘gamma rays beta particles and electrons" Protons (1-2 MeV) 15-28 3 ‘Neutrons (energy dependent) 20 - 80 3-20 ‘Alpha particles and fission 60-200 20 fragments HZE space particles 200 - 600 20 {The radiation weighting fetor, i eauvalent othe quality factor, Q ERP, 199) q" | for electrons of all energies except for Auger electrons or tritium betas emitted fiom nuclei bound to DNA for which a higher quality factor may be used. The relative biological effectiveness (RBE) is defined as the empirically determined ratio of the cumulative absorbed dose of reference radiation (or bassline irradiation patter) to the cumulative absorbed dose of a subject radiation (or irradiation pattern) required to ‘Produce an identical level of biological response (during an icentical period of time and other conditions being equal) in u particular experiment, organism, or tissuc, RBE is defined8 Raabe | a Introduction to Intemal Radiation Dosimetry 19 as the dimensionless ratio of the absorbed dose of a reference radiation that produces a specific level ofa specified response to the absorbed dose of a test radiation that produces the same level of the same response; radiation quality is presumed to be the main variable ‘with other factors such a dose distribution, exposure timing, and time to effect kept as similar as possible. Mathematically, RBE can be described by’ Dy (F,)( REFERENCE} ‘DF OLTEST] where Da is the absorbed dose of reference radiation and D is the dose of the test radiation yielding a given response level effect, F, ata time t. BBE (1-25) BE is usually used to contrast high LET and low LET radiation, customarily treating the low LET radiation (such as electromagnetic radiation or beta particles) as the reference radiation. Emphasis is usually on low doses (< 0.2 Gy) with RBE calculated as the ratio of the presumed linear portions of the dose response curves. Of particular concem is the use of the available data and information forthe selection of radiation quality factors, Q, to be used in radiation protection, ‘The radiation quality factor, Q, has been defined to represent in a general quantitative fashion the relative biological effectiveness that might be expected fora given radiation type as a function of LET. From this a biologically equivalent dose can be defined as: H = DON (1-26) where H is the equivalent dose in sieverts (Sv), N is a dose distribution or modifying factor (usually assumed to be exacily 1 or dropped) and the quality factor, Q, has dimension of Sv/Gy. Clearly, the biologically equivalent dose is a non-physical abstraction that should ‘be used with caution in intemal radiation dosimetry. {A functional relationship of radiation quality factor, Q, and unrestricted LET, L, was given by the ICRP (1991), For L<10 keV/um, Q(L)*1. For 10°Py inthe human lung from worldwide fallout. Assume the average person inthe U.S. has a steady-state Iung content of 10 mB. The average alpha particle energy for "*™*Py is 5.15 MeV so that = 5.15 MeV assuming 100% absorption in lung tissue. The mass of the human lang in reference man is 1000 g. After proper unit conversions, Equation (I-27) yields a daily dose rate of 7.1«10-° Gylday. Assuming the content is unchanging, the anual dose would be 7.110" Gy/day ~ 365.25 days = 26x10" Gy = 0.26 yGy. With a autlity factor of 20 Sv/Gy for alpha radiation, the corresponding annual equivalent dose is 52 uSv. This is considerably lower than the normal level of alpha iradiation of the lung that results from the inhalation of naturally occuring radon decay products inthe ai. Importance of progeay and mixtures, Radiosctive decay products are frequently responsible for a greater portion ofthe dose delivered after radionuclide intake thn isthe pareat, For example, “Y, the 64-hour half-life daughter of Sr, quickly reaches socular ‘equilibrium and delivers a high energy beta particle with peak energy of 229 MeV. In contrast, the peak energy of the beta particle emitted by "Sr is only 0.55 MeV. Ren, the radioactive progeny display diferent retention kinetics than the paren. The progeny may clear faster and may deposit into a completly different organs. For example, ‘the main dose delivered by ”*Ra deposited in the human skeleton comes from “Rn progeny down to *"Po (Figure 1-1). The mean skeletal dose rate from alpha particle irradiation by “Ra and the appropriate associated amounts of "Rn and progeny at a time t (in days) is given by: 13.8 (E,,+ 7% Em] SBa() | 138 Ep, SBp(6) 29) ne ro where dy(t) isthe alpha radiation dose rate (Gy/day), 13.8 isthe constant of dimensional conversion (Equation 1-27), SB,,(t) [MBq] is the skeletal content of **Ra at time t, r,t) is the fraction as a function of time of the "Rn atoms formed from ™*Ra that decay in the sheleton, Ey, = 4.7 MeV and Ey, = 19.16 MeV are the average energies (MeV) of the tlpha radiation per disintegration of ™Ra and of "Rn in combination with short-lived a9 =2 Raabe progeny (including alpha emitting ?"Po and **Po), Ey, = 5.305 MeV is the alpha radiation energy of ?*Po, SB,x(t) is the total skeletal activity (MBq) of "Po, including that from intakes of "Pb and that from retained radon decay, and m() is the mass in grams of the irradiated skeleton as a function of time post intake, t, in days, The dosimetry for **Ra and progeny has been limited to absorbed alpha radiation because previous work has indicated that the biological responses, per unit of energy, of the amount of low LET radiation and recoil nuclei ere relatively small, compared to the alpha irradiation (Raabe and Parks, 1993) Importance of absorbed fraction, When longer-anged ionizing radiation is emitted by an intemally deposited radionuclide, such as high energy beta particles or gamme radiation, it js necessary to consider the fraction of the radiation absorbed by the specified tissue and delivered to other tissues of the body. For example, a skeletal burden of Sr can be used to calelate a mean skeletal dose rae for beta radiation from "Sr and its decay product °Y, in equilibrium, given by y(t) = 138/00) By. SB (0/00 (30) where 13.8 isthe constant of dimensional conversion (Equation (1-27), dt isthe daily dose rate (Gy/day), SBy(t) isthe skeletal content of "Sr in MBG, Eyay = 1:13 MeV is the average energy of *'Sr-+"°Y beta radiation per disintegration of "Sr, f(m) is the fraction of beta radiation absorbed by the skeleton as a function of skeletal mass, and m() is the mass G ofthe irradiated skeleton asa function of elapsed time, t, in days (Raabe and Parks, 1993), For adult person f(m) is about equal to 0.95. Dosimetrie Models and Limits of the ICRP ‘The International Commission on Radiological Protection has developed elaborate and detailed dosimetric models for essentially all of the important radionuclides to which people might be exposed (ICRP, 1979). These include complete physical, anatomical and biokinetic ‘models for the respiratory tract, the gastrointestinal tract, and the skeleton. In the recommendation of the exposure standards, the ICRP has used the absorbed dose to calculate an equivalent dose for non-stochastic somatic effects withthe quality factors (now called radiation weighting factors) given in Table 1-3, Non-stochastic somatic effects are those such direct radiation injury or ocular cataracts in which the non-neoplastic effect is the result ofthe accumulated damage to tissue. A threshold for adverse response is assumed to exist for non-stochastic effects, Based upon the dosimetric models, the ICRP assigns expected equivalent doses to body organs and tissues for every year up to 50 years after an intake oceurs, The sum of these expected doses for 50 years is called the committed ‘equivalent dose (Hy). The committed equivalent dose limit recommended by the ICRP for ‘Introduction to Internal Radiation Dosimetry 2B ‘occupational exposure to ionizing radiation to limit stochastic effects is 0.5 Sv for any tissue for organ of the body (ICRP, 1979). In rocommending, standards to limit radiation induced cancer and mutation, which are tssumed to be stochastic (statistically random) effects, the ICRP assigned 2 relative carcinogenic susceptibility factor to the major organ systems of the body, called the tissue weighting factor (;) having units of Sv/Sv, to describe all stochastic, potentally-adverse effects. The tissues weighting factors are normalized to unity for all organs and tissues in the human body. The tissue weighting factors are primarily based upon the relative frequency of radiation-induced cancer by organ system observed in the Japanese atomic ‘bomb survivors. The product of the equivalent dose to tissue, Hf, in Sv and the tissue ‘weighting factor yields the effective dose in Sv (wyH) for stochastic effects. The ICRP tissue weighting factor (w,) are summarized in Table 1-4, The 50-year committed effective dose (rH) limit recommended by the ICRP for occupational exposure to ionizing radiation to limit stochastic effects is 0.05 Sv (ICRP, 1979). Recently, the ICRP has recommended at total effective dose of 0.1 mSy in any 5 year period (ICRP, 1991). However, current standards in the United States are based primarily upon ICRP-26 (ICRP, 1977), Annual Limit on Intake (ALI), The annual limit on intake (ALI) of a form of radionuclide is a secondary limit designed to meet the basic dose limits for occupational exposure. Intakes below the ALI will not be expected to yield committed equivalent or effective doses in excess of either the non-stochastic or sfochastic limits for any organ or tissue. Radionuclide forms included in the ALI calculation are Class ¥ (dissolves in years), which are considered extremely insoluble, Class W (dissolves in weeks) which are considered moderately insoluble, and Class D (dissolves in days), which are considered moderately soluble Derived Air Concentration (DAC). The ICRP has calculated a derived air concentration (DAC) for each radionuclide form by assuming uniform exposure of workers for 2000 hours per year to inhaled airbore radionuclides at a concentration that would preclude intakes in excess of the appropriate ALI, The result is given by: DAC = ALI/(2000x600.02) = ALI/(2400) Baim? a3) ‘here 2000 hr is the number of work hours per year, 60 min is the number of minutes per hour, and 0.02 m*/min is the minute volume air breathed at work for reference man under conditions of light activity. The cumulative inhalation exposure, DAC-hours, describes the amber of hours of exposure times the air concentration as a fraction of the DAC.i@ 4 Raabe ‘Table 1-4. Stochastic effect tissue weighting factors assigned by the | Intemational Commission on Radiological Protection in ICRP-60." Tissue/Organ ws (SviSW) | “Gnas s—“SsOSSSCSsSCSC‘“‘C SS Stomach 012 Colon 012 Lung (bronchial epithetium) 0.12 (0.08) Red bone marrow 02, Breast 0.05 Esophagus 0.05 Bladder 0.05 Liver 0.05 ‘Thyroid 0.05 Bone surfaces 0.01 Skin oor Remainder 0.05 “Adapted ffom ICRP-60 (1991, diferent values ae used in IORP-30 (1979) "Applied to the mean equivalent dose over the entire skin SUMMARY Internal radiation dosimetry is the scientific methodology used to measure, calculate, estimate, assay, predict, and otherwise quantify the radiative energy absorbed by ionization of atoms in human tissues as a result of emission of energetic radiation by internally deposited radionuclides. Factors that are important include (a) identification of the target tissue, (b) the physical, chemical and biokinetic properties of the radionuclide forms, (© specification ofthe dose rate as well a the absorbed dose, (A) geometrical relationships of intemal radionuclide sources and target tissues, (@) isotopic purity and composition of radioactive materials, (2) irradiation pattems and seperate behevior of radioactive decay products, and (g) fractions of radiant energy deposited in target organ or specified tissue. Conversion of absorbed dose to equivalent dose, effective dose, or any other non-physical Introduction to Intemal Radiation Dosimetry 23 or biologically modified quantity is not the primary purpose of intemal radiation dosimetry, bot is necessary for demonstration of compliance with State and Federal regulations. REFERENCES Chase, G.D.; Rabinowite, JL. Principles of Radioisotope Methodology, 2nd Ed. Burgess Publishing Co., Minneapolis; 1962. Evans, RD. The Atomic Nucleus. McGraw-Hill Book Company, New York; 1955, ICRP. Task Group Report on Reference Man. Publication 23, Pergamon Press, Elmsford, NY; 1975, ICRP. Recommendations of the International Commission on Radiological Protection. Publication 26, Pergamon Press, Elmsford, NY; 1976. ICRP. Limits for Intakes of Radionuclides by Workers. Publication 30, Part 1, Pergamon Press, Elmsford, NY; 1979. ICRP. Radionuclide Transformations, Energy and Intensity of Emissions. Publication 38. Pergamon Press, Elmsford, NY; 1983, ICRP. 1990 Recommendations of the International Commission on Radiological Protection Publication 60, Pergamon Press, Elmsford, NY; 1991 ICRU. Linear Energy Transfer. Report 16, International Commission on Radiation Units ‘and Measurements, Washington, D.C; 19703. ICRU. The Quality Factor in Radiation Protection. Report 40. international Commission ‘on Radiation Units and Measurements, Washington, D.C.; 1970. ICRU, Conceptual Basis for the Determination of Dose Equivalent. Report 25. International ‘Commission on Radiation Units and Measurements, Washington, D.C.; 1976, ICRU. Quantitative Concepts and Dasimetry in Radiobiology. Report 30. International Commission on Radiation Units and Measurements, Washington, D.C.; 19803, ICRU, Radiation Quantities and Units. Report 33. International Commission on Radiation Units and Measurements, Washington, D.C.; 1980b.26 Raabe ICRU. Quantities and Units in Radiation Protection Dosimetry. Report 51. International ‘Commission on Rediation Units and Measurements, Washington, D.C. 1993, Lederer, C.M.; Shirley, V.S. Table of Isotopes (7th Edition). John Wiley & Sons, Inc., New York, 1978, NCRP. Si Units in Radiation Protection and Measurements. Report 82, National Council ‘on Radiation Protection and Measurements, Bethesda, MD; 1985. NCRP. The Relative Biological Efectiveness of Radiation of Different Quality. Report 104 National Council on Radiation Protection and Measurements, Bethesda, MD; 1990, Raabe, 0.G.; Parks, N.J, Skeletal uptake and lifetime retention of *S+ and Ra in beagles. Radiation Research 113: 204-218; 1993. Wyckoff, H. 0. Historical development of radiation dose quantities and their units, ‘presented at the 1983 Health Physics Summer School, Baltimore, MD; 1983. Chapter 2 PHYSICAL AND CHEMICAL INTERACTIONS OF RADIATION WITH LIVING TISSUES Wesley E. Bolch ee OVERVIEW Radiobiology studies clearly indicate that radiations of difeing type vary in their ability {o induce biological damage per unit sbsorbed dos to irradiated tissues. These differences an, 10 a large extent, bo related to the three-dimensional structure of ionization tacks produced by charged particles traversing tissue volumes of intrest. Furthermore, charged- aricle tack trcture plays an important role in not only in the ability ofthe particle to induce direct ionization damage to cxlular targets, bat in its ability to produce damage indirectly via the creation of fice radicals inthe cell envionment. In this chapter, the fundamental of charged panicle interactions are reviewed, followed by a summary ofthe ‘adiaton chemistry of pure water, a typically surogate for soft tinue. The chapter onclides with a brie discussion of factors relevant to the radiation chemisty of the tissue environment MECHANISMS OF ENERGY TRANSFER BY CHARGED PARTICLES Jn the vast majority of internal dosimetry caledlations, only thee types of radiations are generally considered: photons, electrons (both postive and nogaive), and alpha particles. Photons are classified as indirectly ionizing radiation in that essentially all of the energy transfers to irradiated tissue are produced by electrons and/or positrons created in photon brortion events (photoelectric and pir-production interactions) or scattering events (Compton interactions). Auger electron emission might alo fellow orbital vacancy filling of ionized target toms (Attix, 1986; Evans, 1982) Consequently, one can focus exclusively on the interactions of charged-particles (directly ionizing radiations) for a better understanding ofthe basis of tissue effets from intemal exposures. ‘A charged-particle transfers its kinetic energy to tissue through electrostatic Coulomb force Interactions with practically every constituent tissue atom in its vicinity. Thete forces may are concentratod on citer the atom as a whole or its nuclei. Most interactions result in the temsfer of only a small fraction of the particle's kinetic energy (10 to 100 eV) Consequentiy, many collisions are necessary to comploely stop a charged particle, For28 Bolch ‘Physical and Chemical Interactions of Radiation with Living Tissues 29 example, a 1-MeV particle would participate in approximately 10° to 10* energy transfers in order to expend its entire initial kinetic energy. ‘The type and nature of each energy transfer is dictated primarily by the particle's impact ‘parameter defined as the nearest distance between the path of the charged particle and the nucleus of the target atom to which energy is transferred. A "sofi" collision is sad to occur when the impact parameter greatly exceeds the size of the target atom defined by its classical atomic radius, Here the Coulomb force influences the atom as a whole and a small amount of kinetic energy (a few eV) is lost in the interaction. The result will be either an ionization or excitation depending upon the amount of energy transferred and the electron binding energies of the target atom. Since most atoms in the vicinity of a meving charged particle will be located at relatively large impact parameters, soft collisions account for the ‘vast majority of all interactions. Furthermore, since the energy lost per collision is small, soft collisions account for approximately one-half of the total kinetic energy lost as the particle stops in the medium, With far less frequency, a charged particle may pass a given target atom with an impact ‘parameter comparable to the radial dimensions ofthe atom. In this ease, the Coulomb force is concentrated on a single orbital electron and may result in a relatively large energy transfer. While few in number, these “hard” collisions account for the remaining one half of the total energy lost by a stopping particle, Hard collisions result almost exclusively in ionizations, The electron ejected in the process is termed a "secondary" electron, In cases where the ejected electron has sufficient kinetic energy to produce its own distinct ionization track, itis referred to as a “delta-ray*. Each of the secondary and higher order clectrons will quickly lose their kinetic energy to the absorbing medium in additional nizations or electronic excitations until their energy falls below the lowest electronic excitation potential available in the medium. At this point, all electrons are collectively ‘termed subexcitation electrons, Radiation chemists occasionally utilize an alternate classification for energy-loss events. In this scheme, energy-loss events of less than 100 eV are referred to as "spurs". When the energy loss is between 100 eV and 1 keV, a "blob" is said to have been formed, Finally, “short-tracks" or "deltaays" are the result of energy transfers exceeding 1 keV (Spinks and Woods, 1976), Finally, when the impact parameter of the charged particle is much less thar the radius of a target atom, the Coulomb-force interaction is concentrated on the nucleus. In all but 2-3% of these nuclear interactions, the charged particle is elastically scattered and kinetic energy is lost by the electron as needed to conserve momentum. Because the electron’s rest mass is very small compared to that of the nucleus it encounters, this energy loss is relatively insignificant. Consequently, the primary result of an elastic collision isan angular deflection of the particle, These deflections can be considerable for particles of small rest mass (ie., tlectrons and positrons), but are insignificant for heavy particles (Le, alpha particles) except tthe very end of their ionization tracks when their velocities are small. The microscopic Gross section for elastic collisions is proportional to the square of the atomic number of the absorbing medium; thus one would expect electron ionization tracks to appear more tortuous in say bone tissue than in soft tissue due to the higher effective Z of bone. tn the remaining 2-3% of charged-particle interactions with atomic nuclei, the particle ‘undergoes an inelastic radiative collision in which it is not only deflected, but may lose up to its entire residual kinetic energy in the form of an x-ray photon. This continuous distnbution of x rays is collectively termed bremsstrahlung, or "braking radiation”. As with Glastic collisions, the microscopic cross section for bremsstrahlung production is proportional to the square of the atomic number of the absorbing medium. Additionally, the cross section is inversely proportional to the square ofthe rest mass of the charged particle. Consequently, bremsstrahlung is once again important in internal dosimetry only for electron and positron energy loss in bone tissue, (CHARGED-PARTICLE TRACK STRUCTURE In its most general definition, a charged-particle track is defined as the spatial location of every excitation, ionization, and subexcitation electron produced in the wake of a passing charged particle. It is now generally believed that biological effects of radiation can be related to the three-dimensional structure of the charged-particle tracks involved in the initial damage to sensitive subcellular targets such as genetically coded nuclear deoxyribonucleic acid, DNA. This linking of biological effects to track structure forms one of the central research goals of microdosimetry (Turner et al, 1988). Even within the applied area of radiation protection, however, a very simple one-dimensional indicator of track structure is invoked within dosimetry calculations: linear energy transfer or LET. The linear energy transfer ofa charged particle isthe average instantaneous rate of enerzy loss to ionizations and excitations per unit pathlength and is typically expressed in units of (MeV ca) or (keV pm). Iti equivalent tothe term linear collisional stopping power commonly used in physics. There are three key qualifiers to this quantity. First, itis the average quantity such that any given charged particle of equal kinetic energy mey experionce a linear rate of energy loss greater than or less than this value. Second, LET is function of particle velocity and thus asthe particle losses energy, is linear rate of energy loss changes, Finally, LET is used to describe energy deposition local to the charged- Paticle track and thus it does not include energy loss due to bremsstrahlung production= 30 Bolch Most tabulations of LET are expressed in terms of mass collisional stopping powers or average rates of energy loss per unit density thickness. Here the units are typically MeV per ‘a per em?, For heavy charged particles such as alpha particles, the mass collisional stopping power can be estimated by the expression: ( (ar ) 4nrime7N, (Poe ey pai), BF a where dT is the kinetic encrgy lost in the traversal ofa short distance pis the physical density of the medium, N, isthe electron mass density of the absorbing medium, ris a constant called the classical electron radius (2.818 x 10°? cm), m,c’ is the rest mass of an clectron (511 keV), 2 is the particle charge (equal to its atomic number if the particle is a fully tipped of its orbital electrons), 6 isthe particle velocity relative tothe speed of light in vacuum, and I is the mean excitation energy of the absorbing medium. Equation (2-1) shows that in a given medium such as sof tissue, there are only two characteristics of the charged particle which dictate its rate of energy loss: the particle's velocity and its charge Itis a common mistake to think that a particle's mass determines its LET; mass enters the picture only as the physical link between kinetic energy and particle velocity. It is not surprising then that velocity and charge are involved when one considers that energy loss events are the result of Coulomb-fore interactions. Conceptionall, the ability of a charged patticle to transfer its kinetic energy to given target atom should depend primarily upon on (1) the magnitude of the Coulomb force exerted (whichis proportional to the square of the particle charge) and (2) the length of time the particle is in the vicinity of the target atom. This time of interaction, of course, increases as the panicle velocity decreases Figure 2-1 shows the LET of alpha particles in liquid water as a function of kinetic energy. In many applications in radiation dosimetry, liquid water is used as a surrogate for soft tissue. As an alpha particle slows down, its linear rate of energy loss increases to a ‘maximum value referred to as the Bragg Peak. This tumover in LET is not predicted by Equation (2-1) which indicates that LET increases without limit as the particle slows down. ‘The discrepancy lies in two phenomena which are not considered in the derivation of Equation (2-1), First, as the alpha particle velocity becomes comparable to the velocity of «given subset of electrons in the target atoms, those orbital electrons cease to participate in the transfer of energy. Consequently, since K-shell electrons have the highest velocities, they are the first to be withdrawn from the process. With fewer electrons participating in energy transfers as the alpha particle slows down, the average rate of energy loss to the modium consequently decreases. Correction terms may be added to Equation (2-1) to ‘compensate for this reduction in target electron population. The second phenomenon is more difficult to correct for. It involves the attachment, release, and reattachment of free electrons to the alpha particle at low velocities. With the addition of a free electron, the alpha particle's effective charge is reduced from +2 to +1, This reduction in charge reduces the Physical and Chemical Interactions of Radiation with Living Tissues 31 1 1 Linear Energy Transfer (keVium) es 1eos E04 1E03 102 1E41 “TE00 E01 1Ee02 E08 Particle Kinetic Energy (MeV) Figure 2-1, Linear energy transfer (LET) of alpha particles and electrons in liquid water Coulomb force exerted on the m: in Equation (2+1)] ia and thus the particle's LET by a factor of four [2 term Figure 2-1 also shows the LET of electrons as a function of their kinetic energy. Whereas the Bragg. peak value of LET for alpha particles occurs at ~ 725 keV, the Bragg peak for lectrons occurs at ~ 100 eV, While electrons are generally considered to be low-LET radiations, Figure 2-1 shows that low-energy electrons can actually ackieve ionization densities comparable to both low-energy (~ 1 keV) or high-energy (~ 10 MeV) alpha particles. One must realize, however, that a 100-eV electron will produce at most only a single spur, ‘whereas the alpha particle tracks will produce a linear column of spurs and blobs of comparable ionization density ‘An additional feature of Figure 2-1 is indicated by the two horizontal lines at LET values of 35 and 175 keV um”. These LET values delineate the range over which the quality factor varies from a minimum value of | to a maximum value of 20 as defined in ICRP Publication 26 (ICRP, 1977). Note that ifa given internal exposure involves relatively low= energy electrons (such as for an Auger-clectron emitter incorporated within DNA), quality factors exceeding 1.0 would be appropriate. Similarly, high-energy alpha particles with32 Bolch kinetic energies exceeding ~ 300 MeV (as would be'seen in galactic cosmic rays) produce ionization tracks with linear densities comparable to low-LET electrons. Another way to view the changes inthe rate of energy loss as a particle slows down is to plot the particle's LET versus depth in tissue. Figure 2-2 shows such a curve for 5-MeV alpha particles, The total range of the particle is ~ 38 ym in tissue. At the beginning ofthe ionization track, the alpha particle loses energy at ~88 keV jim" with an asociated quality factor of 14. It is not until a tissue depth of ~ 28 wm (~ 74% ofthe entire ionization track) does the alpha particle experience an LET exceeding 175 keV jm” where the cuslity factor plateaus at 20. Consequently, applying a quality factor of 20 to all values of absorbed dose Aeliverd by 5-MeV alpha particles will in fact rerult in @ conservative extimate ofthe dose equivalent, ‘While linear energy transfers a convenient parameter for quantifying track stuctur slong the axial direction of the charged particle (Le, slong its path-length), it provides litle information as to the ability ofthe charged particle to impart energy inthe direction radial to its pathlength. For example, consider a 5.51-MeV alpha particle and a 804eV proton in tissue. At these kinetic energies, the alpha particle is traveling at a velocity such that its value of B is 2.94993 x 10 and that of the proton is 1.70302 x 10~. The alpha particle Linear Energy Transfer (keVinm) OEE EEE EEE EERE EERE EEE os) ww Depth in Tissue Qu) Figure 2-2, Linear energy transfer (LET) of a 5-MeV alpha particle as a function of dopth in tissue showing the Bragg peak near the end of the path. Physical and Chemical Interactions of Radiation with Living Tissues 3 js traveling at s higher velocity than the proton and thus its interaction time per target atom jeless. At the same time, however, its higher charge generates a stronger Coulomb force wich exactly compensates forthe shorter interaction time. The net influence of each of the particle's charge and velocity is such that both the alpha particle and proton transfer their Kinetic energy st the same rate; both experience a linear energy transfer of roughly $2.6 keV um’, But what about their ability to impart energy in the radial direction? For heavy charged-partcles the maximum energy which can be transferred in a partcle- clectron interaction (and thus the maximum energy delta-ray which may-be produced) is shown to be a function of only the particle velocity eame?( aa as = 2m (S = ea) ‘Substituting into Equation (2-2) the values of B* for each particle, one sees that the alpha parc can produce dele rays up to~3 keV in energy, whl the slower moving proton can nly produce at most a 174V secondary electvoa. Consequently, the ahs parce prodvecs on average © much "wider track than tat ofthe equivalem-LET proton with Fesard 1 the energies and ranges ofits secondary electrons ‘Another important statement on the structure of charged-particle tracks is evident from Equation (2-2), As an alpha particle or any other heavy particle slows down in tissue, its velocity decreases and, sccording to Equation (2-2), its maximum ability to tansfer its kinetic energy also decreases. Ina three-dimensional sense, the ionization tracks of heavy charged-pasticles not only increase in density as the particle approaches its Bragg pesk, but the track thins out as the particle slows down giving it a conical appearance. The fact that alpha particle ionization tracks appear conical has important implications in research areas such as microdosimetry as well as applied areas such as the interpretation of track-etch ‘measurements of alpha-particle emitting radon daughters. PRODUCTION OF FREE RADICALS IN LIQUID WATER ‘As a charged particle traverses a small microscopic volume of tissue, the physics of energy H+-0n es) The H-atom is also called the H radical indicating that it too has one unpaired electron Depending upon the particular excitation states involved, less probable fates of the excited ‘water molecule include a delayed ionization followed by Equations (2-3) and (2-4), an altemate dissociation in which H, and an O-atom are formed, or @ relaxation of the excitation energy resulting in no free radical production, ‘Physical and Chemical Interactions of Radiation with Living Tissues 35 ‘At one picosecond following the passage of a charged particle in a microscopic tissue Volume, the ion track consists of a collection of free radicals (OH, Ht, and e,¢) and thydronium ions (H,O") whose three-dimensional structure is determined primarily by both the LET and velocity of the passing ion. This early spatial pattern of chemical species ‘within the track plays a critical role in determining the fraction of free radicals which ‘undergo chemical reactions within the track (intratrack reactions) and the fraction which diffuse away from the track core to participate in reactions outside the track (intertrack reactions) including those with biological targets such as DNA. CHEMICAL REACTIONS OF FREE RADICALS IN LIQUID WATER The chemical stage of track development within a microscopic tissue volume primarily ‘cocurs between 10" s and 10% s following the passage of the original charged-particle (electron or alpha particle). During this time, free radicals and other species in the track ‘ndergo diffusion from regions of higher concentratian (individual spurs for electrons and the track core for alpha particles) to regions of lower concentration (water regions surrounding the spurs or tack core). As a result, the charged-particle track becomes more ‘and more diffuse overtime until epproximately one microsecond when the structure of the track is lost and a more or less homogencous distribution ofthe unreacted radicals remains (Fumes etal, 1988). The thermal motion of chemical reactants can be viewed on a molecular level as diteste Aisplacements or jumps" between surounding watr molecoles, Starting with Fick’ first law of diffusion, one can atcribe a root-mean-square distance € which is traveled by © reactant during a jump time + according tothe relation af es) or her is the experimentally determined diffusion coefficient forthe reactant of interest. Valucs of A Gin units of 10° em? s) are 80, 8.0, and 25 in liguid water forthe H radical, hydrated clctron, and OH radical, rorpetively” According to Equation (2-6), the mean distance H radical could diffuse in water over the time period 10°" s to 10% s would be ~ 69 nm or approximately 24 water molecule diameters. In that same time interval, the hydrated closion would rave only~5.8 nm and the OH radical would diffs only ~ 3.9m During their diffusive motion, however, the water radicals are subject to an array of hemical reactions either between themselves within the track (intratrack reactions) of with solute molecules (eg, dissolved oxygen). Four rections which occur inthe track result in the reconstttion of water molecules: HOH + HO en36 Bolch rag t HO" = H3H,0 as) qq OH ~ OH es HO" + OH ~ 28,0 In Equation (2:9), hydrated electrons react with OH radicals to form hydroxyl ions which then combine with hydronium ions in Equation (2-10) to reconstitute two molecules of ‘water. Four additional reactions possible within the track involve the formation of molecular products H, and H,0; @.10) tag + H+ H,O ~ Hy + OH” @an He HoH, @12 “OH + OH ~ H,0, 13) From Equation (2-13) one might suspect that the intratrack production of hydrogen peroxide, a highly unstable oxidizing agent, might be the source of chemical damage to sensitive cellular targets such as DNA. This is generally not the case in that the yield of H,0, is relatively small and the cell contains # host of enzymes designed to decompose H,0, and other peroxides produced during the natural course of cellular metabolism. It is the free radicals themselves, particularly the OH radical, which initiate indirect damage to the DNA molecule. Itis possible to experimentally determine the relative number of free radicals produced with a chargei-particle track with a special technique called pulse radiolysis (Spinks and Woods, 1976). In these studies, sample cells of pure water are irradiated by a pulse of high-energy electrons from a linear accelerator. At the same time, a portion of the beam is intercepted by «call containing 1 atm of xenon in which Cerenkov radiation is generated for wee a8 48 analyzing light source. By delaying the Cerenkov light and focusing it on the sample cell normal :o the incident beam, the relative absorbance of free radicals is measured as a function of time following the arrival of the electron pulse. With proper calibration of the data, quantitative yields of the various free radicals can be determined as functions of time. Figure 2-3 shows the results of pulse radiolysis measurements of OH radical and hydrated electron yields for pulsed beams of high-energy electrons (Jonah et al, 1976; Jonah and Miller, 1977; Sumiyoshi and Katayama, 1982). Radiation chemists conventionally quote radiation chemical yields in terms of G values defined as the number of species formed (or present) per unit energy deposition by the incident radiation. Note that G values are analogous to the W value (eV per ion pair formede in air by ionizing radiation) used in the design and study of radiation detectors. In keeping with the radiation chemist’ concept of Physical and Chemical Interactions of Radiation with Living Tissues 37 G value Me MEO IESE ET Time (6) Figure 2-3. Time-dependent yields of OH radicals and hydrated electrons in liquid ‘water as determined from pulse radiolysis measurements with high energy electrons. the track spur, the normalizing unit of energy depotition is 100 eV. In this definition, G values at very early times within the track give an estimate of the average number of species produced within a spur, For example, the Japanese study in 1982 found that there ‘were ~ 4.8 OH radicals present per spur 30 picoscconds following the inital passage of the leciron beam (see Figure 2-3) This interpretation of the G value is not valid for times significantly grater than 10™ sin that spurs ae no longer clearly identified due to thermal diffusion of the track species and the coresponding loss of track structure overtime AAs shown in Figure 2-3, G values for various chemical species are functions of time, By extrapolating the data of Figure 2-3 back to the beginning of track development (i¢., at one Picosecond), one can estimate that the intial yield of OH radicals is~ 7 radicals per spur and the initial yield of hydrated electrons is ~ 5 radicals per spar. As the track develops over time, Equations (2-7) to (2-13) indicate a net consumption of these free radicals with a corresponding production of molecular products. Nevertheless, as the track expands over Sime, edditional intratrack reactions become increasingly improbable due to the larger and larger spatial separation of unreacted radicals remaining within the track. This tumover in the rate of decrease in radical yields is shown in Figure 2-3 forthe hydrated electron data where an inflection point is evident at ~ 1 ns. Extrapolating the data forward in time, we soe38 Boleh that a somewhat steady-state yield of between 2.5 ad 3 is achieved for both the OH radical and the hydrated electron. How does track structure influence the steady-state yield of free radicals? Clearly, as the LET of a charged particle increases, the spatial separation of individual spurs decreases, Consequently, as a free radical escapes its spur of origin, it is much more likely to encounter free radicals from a neighboring spur within a high-LET ion track than within a ow-LET ion track. Furthermore, the number of radical reactions per unt time should increase with increasing track LET and thus the microsecond yield of free radicals should comespondingly decrease and the yield of molecular products should correspondingly ‘This pater is exactly seen in the experimental data showa in Table 2-1. The first radiation type listed is ®Co gamma-rays which produce a distribution of electrons vie Compton and phoroclectric events in water. The overall track-average LET experienced by this distibution of electrons represents a value lower then thet seen in either the 32-MeV or 12-MeV alpha particle tracks. From the early discussion of collision stopping power, itis clear that the higher-onergy alpha particle displays a lower track-average LET than that displayed by the 12-MeV particle. The radiations are thus listed in Table 2-1 in order of incrssing LET. Here we see that the steady-state yield of OH radicals decreasing from ~ 287 OH radicals per 100 eV for “Co irradiation to an average of only 0.54 OH radicals per 100 eV for 12-MeV alpha particles, The corresponding yields of hydrogen peroxide incrase from 0.61 t0 1.08, respectively. Table 2-1. G values for various species produced in the radiolysis of water by radiations of differing LET. (Source: von Sonntag, 1987). - OH H. HO, Co prays 287 270 061 0.61 043 32MeV o-particles 0.97 on 0.42, 1.00 096 12MeV a-particles 0.54 042, 027 1.08 LL ‘TRACK CHEMISTRY WITHIN THE CELL ENVIRONMENT ‘The development of charged-partcle tracks in tissue differs substantially from that discussed above for pure water irradiations. This difference arses primarily due to the presence of free radical scavengers, molecular oxygen, and various biological target molecules such as DNA. Free radicals are common products of cellular metabolism and thus cells have developed host of enzymes which remove free radicals from the cytoplasm and possibly the ‘Physical and Chemical Interactions of Radiation with Living Tissues 39 ‘pucleoplasm. The scavenging capacity ofthe cell (defined as the product of the scavenger ‘eoncentration and the rate constant for is reactions) is sufficiently high such thatthe mean lifetime of water-

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