Physics

NUCLEAR MEDICINE IMAGINGandTHERAPY

EQUIPMENT FOR SCINTIGRAPHYThe gamma camera does not produce radiation, it detectsthe radiation emitted from within the patient’s body

NUCLEAR MEDICINE DETECTORS1) ANGER CAMERA PRINCIPLE(SINGLE PHOTON SCINTIGRAPHY)

IN NUCLEAR MEDICINE WE USERADIOPHARMACEUTICALS:Organic or Inorganic Molecules labeled withRADIOACTIVE ATOMS

HISTORICAL INFORMATION

HIPPOCRATESFather of RationalMedicineHISTORYDEMOCRITOSFather of the AtomicTheory of the MatterEPICUROSFather of Nuclear Scienceand Nuclear MedicineThe Miracle of the 5 th Century BC

HUMAN PROGRESS1) SURVIVAL: personal LABOR, use of ANIMALS (and later SLAVES)2) PRIMITIVE SCIENCE: OBSERVATION / primitive MACHINES2) WONDER/QUESTIONS about the WORLD AROUND/INSIDE USa) MYSTICISM: MYTHS about GOD(S), POWERS, DEMONS, DEVILS“Theory” of INTELLIGENT CREATIONRELIGIONS (PROPHETS, SAINTS, PRIESTS, PREACHERS)b) RATIONAL THINKING: REASON, DIALECTICSPHILOSOPHY- PHILOSOPHERS / THEORIES (ATOMIC)3) ADVANCED SCIENCE: EXPERIMENT/THEORIES – EVOLUTION4) SEPARATION OF SCIENCE FROM PHILOSOPHY5) INTRODUCTION OF COMPUTER/GENETICS

SCIENCEScience deals with known factsPhilosophy with speculation (theories)

THE FIRST PHILOSOPHERSObservation: Ice Water VaporTheory: Change is a rearrangement of atomsthat remain themselves unchanged

THE FIRST PHILOSOPHERS LIVED HEREANCIENT GREECE

THE FIRST PHILOSOPHERS LIVED HEREANCIENT GREECE

DEMOCRITOSFather of the Atomic Theoryof the Matter“The World Outside and theWorld Inside Us is made ofsmall invisible, indivisibleand indestructible Particlesthe Atoms”

PLATO’S THEORY OFGEOMETRICALOR MATHEMATICAL ATOMISMTHEORY OFTRANSFORMATIONOUT OF THE ELEMENTALTRIANGLES WE CANRECONSTRUCT FOUR OFTHE FIVE REGULARSOLIDSTHE ELEMENTALTRIANGLES ARE THECOUNTERPARTS OF THENUCLEAR OR SUBATOMICPARTICLES

Philosophy and Sciencethrived in the Roman Empire(Greco-Roman civilization)DE RERUM NATURAby Lucretius CarusIn this poem he reviewsthe ancient philosophersof the classical and theroman periods

EPICUROSA PHILOSOPHER OFTHE ROMAN PERIODFather of Nuclear Scienceand Nuclear Medicine“The Atoms may pass throughan Unstable Phasebefore they are stabilizedin their perpetual form”

RATIONAL THINKING:Epilepsy:“...It is not in my opinion any moredivine or more sacred than otherdiseases, butit has a natural cause……It is also curable, no less thanother diseases…….”HIPPOCRATESRELIGIOUS THINKING:“ Epilepsy is the result of effect ofthe gods or the devils ”

ALEXANDER THE GREAT EXPANDED EASTALEXANDER’S EMPIRE

CLASSICAL CIVILIZATION WAS ALSOTRANSFERRED WESTTHE ROMAN EMPIRE

THERE FOLLOWS CHRISTIANITYAND THE MEDIEVAL TIMESBYZANTIUM IN JUSTINIAN TIMES

CHRISTIANITY AND THE MEDIEVAL TIMESSCIENCE ANDPHILOSOPHY BECAMEPART OF RELIGIONFOOT TRANSPLANTATION BYST. ANARGYROI

THE MEDIEVAL TIMESCHRISTIANSMUSLIMS

THE ARABS SOMEWHATPRESERVED AND ENHANCED CLASSICALCIVILIZATION

THE RENAISSANCEIN THE 14 th CENTURYREVITALIZEDSCIENCEandPHILOSOPHYLEONARDO DA VINCI: LA GIOCONDA

HISTORYIt took more than 2000 years for Science to RecoverModern Atomic TheoryJohn Dalton 1880Discovery of Natural and Artificial RadioactivityHenry Beckerel 1896 Marie Curie 1897

HISTORYDmitry Ivanovic Mendeleyev 1896The Periodic Table of the Elements

RADIATION FROM RADIUMTHE UNSTABLE RADIOACTIVE ATOM WAS DISCOVEREDThe Atom is not indistructible

RADIATION FROM ELECTRONSTHE DISCOVERY OF THE X-RAYS

HISTORYTheory of Relativity 1905-1916Albert EinsteinAlbert Einstein:1905 Mass and energy are interchangeableSpecial Theory of Relativity (Space-Time)1907 E=mc 2 - Photoelectric Effect1916 General theory of relativity

MEDICINE LAGGED BEHIND

MEDICINE LAGGED BEHINDKING CHARLES II (17 th century)in hisTUBERCULOSIS CLINIC“healed” patients by placing his hands on their chest(what about some current healers?)

THEORIES ABOUTTHE STRUCTURE OF THE ATOM

MODERNS TIMESSCIENCE PHILOSOPHY and ART returned to the CLASSICSTHE CURRENT PRACTICE OF MEDICINERational decisions based on observation and experimentPrevention and Treatment“…Epilepsy has a natural cause….It is also curable….”“…Protecting and Developing Healthmust rank even above that of restoring it”

MODERNS TIMESSCIENCE PHILOSOPHY and ART returned to the CLASSICSMODERN ARTLes Bourgeois de Calais by RodinSculpture by Colder

MODERNS TIMESSCIENCE PHILOSOPHY and ART returned to the CLASSICSMODERN THEORY about The STRUCTURE of the ATOM

IN NUCLEAR MEDICINE WE USERADIOPHARMACEUTICALS:Organic or Inorganic Molecules labeled withRADIOACTIVE ATOMS

RADIOACTIVE ATOM and RADIATION:radioactive atoms decay and produce radiationa) Particular radiationb) Electromagnetic radiation+e -2 x 511keV photons

RADIOPHARMACEUTICALSOrganic or Inorganic Moleculeslabeled with Radioactive IsotopesRadioactive Isotopes decay and emit:Single Photons: γ, x rays (PLANAR and SPECT IMAGING)Antimatter Positrons: e + (POSITRON EMISSION TOMOGRAPHY)Particles: e - (electrons or beta), a++ (alpha) (THERAPY)Low Energy γ, οr e - (IN VITRO STUDIES)

RADIOISOTOPES IN NUCLEAR MEDICINEPATIENT IMAGINGPLANAR AND SPECT:PET STUDIESSINGLE PHOTON γ, x RAYSenergy > 80keV ( 99m Tc- 203 TI etc)POSITRONS e + ( 18 FDG etc)PATIENT THERAPYPARTICULAR RADIATIONelectrons ( 131 I) or alpha particlesIN VITRO STUDIESGAMMA OR ELECTRONSlow energy ( 125 I, 3 H, 14 C)

NUCLEAR MEDICINE IMAGINGSINGLE PHOTON (γ,x)PLANAR /TOMOGRAPHY (SPECT)POSITRON (e + ) EMISSIONTOMOGRAPHY(PET)Single Photon Emmitters:99mTc, 201 Tl, 67 Ga, 131,123 I, 111 InPositron Emitters:18F, 15 O, 13 N, 11 C, 82 Rb, 68 GaAnatomical and FunctionalImagingMetabolic Imagingor Molecular Imaging

SPECTRUM OFELECTROMAGNETICRADIATIONγ-rays, annihilation photonsand x-rayshave the highest frequencyand the shortest wave lengthThey are not visible andneed special equipment fordetection, quantificationand visualizationof their distributioninside the body

IMAGING INTRODUCTION

HISTORYRectilinear Scanner1950 Benedict Cassen invents rectilinear scanner

HISTORYRectilinear Scanner1954 William Myers operates a rectilinear scanner

HISTORYAnger Camera1957: Hal Anger invents gamma camera

HISTORYCyclotronErnest O. Lawrence (1901-1958)

HISTORYPET Scanner

NUCLEAR MEDICINE IMAGINGSINGLE PHOTON (γ,x)PLANAR /TOMOGRAPHY (SPECT)POSITRON (e + ) EMISSIONTOMOGRAPHY(PET)Single Photon Emmitters:99mTc, 201 Tl, 67 Ga, 131,123 I, 111 InPositron Emitters:18F, 15 O, 13 N, 11 C, 82 Rb, 68 GaAnatomical and FunctionalImagingMetabolic Imagingor Molecular Imaging

EQUIPMENT FOR SCINTIGRAPHIC TOMOGRAPHYDEDICATEDSINGLE PHOTONCAMERASDEDICATEDPETCAMERASHYBRIDSPECT/PETCAMERAS

THE COMBINED PET/CT (GEMINI)PETCT

MATTER AND ENERGYATOMS AND RADIATIONS

THE UNIVERSEMATTER (ATOMS etc) ENERGY (RADIATIONS)ATOM : STRUCTURE, PROPERTIES ENERGY: FORMSRADIOACTIVE DECAY: DIAGNOSIS, THERAPYPAIR PRODUCTION: MATTER FROM ENERGYFISSION: ATOMIC BOMB, POWER GENERATIONFUSION: HYDROGEN BOMB, POWER GENERATIONRADIATIONS: GENERATION (NATURAL-ARTIFICIAL)INTERACTION WITH MATTERDETECTION: INSTRUMENTATIONPROTECTION: RADIATION BIOLOGY

THE UNIVERSE

THE UNIVERSE = MATTER+ENERGYMATTER (Atoms /Particles) ENERGY (Radiations)1. ENERGY from MATTER:Radioactive Decay: Diagnosis, TherapyFission: Atomic Bomb, Power GenerationFusion: Hydrogen Bomb, Power Generation2. MATTER from ENERGY :Pair ProductionMATTER: has MASS (unit: g ) M atomic = 1.66 x 10 -27 kgENERGY: E = mc 2 (unit: erg ) c(speed of light)=3 x 10 10 cm/sec

RADIATIONRADIATION DEFINITION:It is a form of energy or matter in motion through spaceIt has an origin and a destination1. Particular Radiation2. Electromagnetic RadiationRADIATION TOPICS:Generation of Radiation (Natural-Artificial)Interaction with MatterDetection: InstrumentationProtection: Radiation Biology

RADIOACTIVE ATOM and RADIATION:radioactive atoms decay and produce radiationa) Particular radiationb) Electromagnetic radiation+e -2 x 511keV photons

RADIATION1) Particular Radiations (mass)Beta (β) particles: Electrons (e - ) NegatronsPositrons (e + )Protons (p + )/Antiprotons (p - )Neutrons (n 0 )Alpha (α ++ ) particles (nuclei of He ++ )Neutrinos ν / Antineutrinos ν(Quarks, Leptons, Bosons, // Strings ? )

RADIATION2) Electromagnetic Radiation(Waves/Photons)( Radio waves / Microwaves / Infrared, Visible,and Ultraviolet Light / X-rays / γ-Rays )E = hν = hc/λh: Planck constant (6.625 x 10 -27 ergs /cycle)ν: frequency (Hz=cycle/sec)λ: wavelength (cm) c: speed of light (3 x 10 10 cm/sec)Unit: eV = 1.24 x 10 -4 /λ (cm)

SPECTRUM OF ELECTROMAGNETIC RADIATION

ELECTROMAGNETIC RADIATION

X-RAY TUBE

X-RAY SPECTRUM

MATTER + ENERGY = THE UNIVERSEMATTER has MASS (unit: g ) M atomic = 1.66 x 10 -27 kgENERGY: E = mc 2(unit: erg ) c light = 3 x 10 10 cm/secRADIATION: Form of energy in motion through spaceHas an origin and a destination1. Particular Radiation2. Electromagnetic Radiation

RADIATION1) Particular Radiation (mass)2) Electromagnetic Radiation (Waves/Photons)

PARTICLES AND RAYS IN MAGNETIC FIELD

THE ATOMELECTRONSNUCLEUS(NUCLEONS)

THE ATOM

NUCLEUSATOMIC # : Z ( p + ), NEUTRON # : N ( n 0 )MASS # : A = Z + N, MASS of nucleus : MAXZ NThe NUCLEAR FORCE is a strong binding forcethat overcomes the repulsive force of the protonsand explains the stability of the nucleusThe mass of the nucleus M is always less thanthe mass of all nucleons A inside the nucleus (M

THE PERIODIC TABLE OF THE ELEMENTS

SHELLS AND SUBSHELLS OF ELECTRONS

ELECTRONSSHELLS: K, L, M, N, O (max 2n 2 electrons / shell )principal quantum numbers (1 to 5 for K to O)SUBSHELLS(ORBITALS): s, p, d, f, g [max 2(2 l+1)e/o]azimuthal quantum numbers l (l=0,1,2…n-1)they represent angular momentum of electronsthe orbital of the lower energy will be filled first(1s

ELECTRONSIN DIFFERENT ENERGY CELLS

X-RAY EMISSION

STANDING PARTICLE WAVES

PARTICLES: MESONS and BARYONS

PARTICLES and ANTIPARTICLES

PARTICLES of the STANDARD MODEL

PARTICLES of the STANDARD MODEL

PARTICLES of the STANDARD MODEL

PARTICLE TRACKS IN BUBBLE CHAMBERParticle detection

NUTRINO DETECTOR

NUTRINOS

RADIOACTIVE DECAY

NUCLEUSZ : ATOMIC # ( p + ), N : NEUTRON # ( n 0 )A : MASS # = Z + N, M : MASS of nucleusAXZ NThe NUCLEAR FORCE is a strong binding forcethat overcomes the repulsive force of the protonsand explains the stability of the nucleusThe mass of the nucleus (M) is always less thanthe sum of the mass of all nucleons (A) inside the nucleus(M

THE PERIODIC TABLE OF THE ELEMENTS

NUCLIDES - ATOMS - ELEMENTSΝuclides: Atomic species with definite number ofp and n arranged in definite orderRadionuclides: Unstable; Radioactive Decay/FissionIsotopes: Same Z(p), different A and N (n)Isotones: Same N(n), different Z(p)Isobars: Same A, different N and ZIsomers: Same Z,N,A but different energy /spinsIsomeric States (psec to years)Metastable States- long lived Isomeric StatesIsomeric Transition Decay 99m Tc 99 Tc

NUCLIDESIsobars (same A, different Z and N)Isotopes(same Z)Isomers(Same Z, N, A)Al 24129ms 2.07sIT 425 β+ 34.------- -------Isotones(same N)

NUCLEUSThere are 3000 nuclides, stable and unstableSTABLE NUCLEI (270 naturally occurring)The stability is dictated by configuration of p and nStable: N/Z=1 in low-Z elements but increases with AEven numbers of protons and neutronsMagic numbers of p or n (2,8,20,28,50,82,126)All stable nuclides fall on or around of theLine of StabilityUNSTABLE and METASTABLE NUCLEINuclides above the LoS are proton rich (β + ,ΕC decay)Nuclides below the LoS are neutron rich (β - decay)

ATOMIC NUMBER V/S NEUTRONS

LINE OF STABILITY, STABLE/UNSTABLE NUCLEI

RADIOACTIVE DECAY(Unstable => Emission => Stable)NATURAL RADIOACTIVITY (Becquerel 1896)ARTIFICIAL RADIOACTIVITY (Curie/Joliot 1934)Bombardment of stable isotopes with particlesCyclotrons and Reactors, 2,700 radionuclidesMODES OF DECAYAlpha Decay ( α ++ ) 222 Rn => 218 Po + α ++Beta Decay ( β − ) 131 I => 131 Xe + β − + γ + νPositron Emission ( β + ) 18 F => 18 O + β + + νElectron Capture ( EC ) 111 In + e - => 111 Cd + x + νIsomeric Transition (IT) 99m Tc => 99 Tc + γ

ALPHA DECAY (α ++ )Heavy Nuclides(x)p (y)n => (x-2)p (y-2)n + αZ Daughter = (Z Parent –2)

ALPHA DECAY (α ++ )Heavy Nuclides (Uranium, Radon, Plutonium)Beryllium-8 is the lightest nuclide with α decay2α = He ++ , range 0.03 mm, gloves stop α4(x)p (y)n => (x-2)p (y-2)n + α ZD=(ZP-2)222 218Rn => Po + α ( 1 - 10 MeV)86 84Therapy8 Be ( Experimental)

ALPHA DECAY

BETA DECAY ( β − = e − )Neutron rich unstable radionuclidesn => p + β − + νZ Daughter = (Z Parent + 1)

BETA DECAY ( β − = e − )Neutron rich unstable radionuclidesn => p + β − + ν , ZD = ZP + 1Transition Energy =( EP - ED) = Eβ − + Eν =EmaxIf the daughter nuclide remains in excited state,isomeric transition (γ -emission) follows131I => 131 Xe + β − +ν + γ (+ E β − + Ε ν )53 54(range of β − in mms, thick plastic shields stop β − )( ν : antineutrino: no charge, negligible mass, spin)Therapy β − ( 131 I, 85 Sr, 32 P, 153 Sm ), Imaging γ ( 131 I)

BETA DECAY

BETA-GAMMA DECAY OF 131 I

EXAMPLES OF

THE ENERGY OF THE BETA PARTICLES

POSITRON DECAY (β + = e + )Proton rich unstable radionuclides with Transition Energy >1.02 MeVTransition Energy >1.02 MeV can generate two β particles:One β − (to combine p + => n o ) and One β + (to be emitted), [2 x 0.511 MeV]p + (+ β − + β + ) => n o + β + + νZ Daughter = (Z Parent –1)

POSITRON DECAY (β + = e + )Proton rich unstable radionuclides withTransition Energy >1.02 MeV can generate two β particles:One β − (to combine p + => n o ) and One β + (to be emitted), [2 x 0.511 MeV]p + (+ β − + β + ) => n o + β + + ν, ZDaughter = (ZParent –1)18F => 18 O + β + + ν (+E of β + => range of β + < 5mm )9 8(ν : neutrino: no charge, negligible mass, spin)but soon there follows:ANNIHILATION: β + (+ e - ) => 2 x 511 keV photons at 180 0(Imaging: Coincidence Detection, PET)

DECAY OF 68 Ga

ELECTRON CAPTURE (EC)Proton rich unstable radionuclides with Transition Energy n o + νZ Daughter = (Z Parent –1)

ELECTRON CAPTURE (EC)Proton rich unstable radionuclides withTransition (excitation) energy usually lessbut may also be higher than 1.02 MeVp + (+e - usually K shell) => n o + ν, ZD = ZP -167Ga + e - => 67 Zn + ν + x-rays ( x = penetrating)31 30A vacancy is created in the shell of captured e - , thenTransition of an Electron from the next upper shell1) Characteristic x-ray of daughter nuclide, or2) Auger Process with Auger e - emission andCharacteristic x-ray from the Auger e - position

ISOMERIC TRANSITION (IT)Nucleus in excited Isomeric/Metastable (m) Energy StateZ Daughter = Z Parent - Energy (γ)

ISOMERIC TRANSITION (IT)Nucleus in excited Isomeric/Metastable (m) Energy StateZD = ZP ( - E)1) Gamma Radiation (γ ) (may occur in steps)99mTc => 99m Tc + γ (γ = penetrating radiation)43 432) Internal Conversion ( transfer energy to a K e - )Conversion Electron (10% in 99m Tc)Conversion Coefficient α = Ne/NγCharacteristic x-ray of daughter nuclide orAuger Process with Auger e emission andCharacteristic x-ray from the Auger e position)

TECHNETIUM-99m DECAY SCHEME

SUCCESSIVE DECAY EQUATIONSWhen daughter radionuclide (D) is produced fromparent (P) and at the same time both decayRate of Growth dN D /dt = λ P N P - λ D N D and(A D ) t = N D λ D = [λ D (A P ) o / (λ D -λ P )] (e −λ Pt -e -λDt )Transient Equilibrium (when λd > λp)Secular Equilibrium (when λd >> λp)

MOLYBDENUM/TECHNETIUM GENERATOR

Mo/Tc GENERATOR

QUANTIFICATION OF RADIATION

EXPONENTIAL DECAY

PHYSICAL HALF LIFE (t 1/2 OR T p )Time required to reduce activity to one halfIndependent of physical chemical conditionsDecay Constant, λ = 0.693/ t 1/2In one t 1/2 A o is reduced to 1/2 A o = A o / 2 1In n t 1/2 A o is reduced to A o / 2 nA t = A o / 2 n = A o / 2 ( t/t 1/2)= A o (0.5) (t/t 1/2)10 t 1/2 reduce A o to 0.1%MEAN LIFE (τ)Average life time of a group of radionuclidesτ = 1 / λ τ = t 1/2 / 0.693 = 1.44 t 1/2

BIOLOGIC (T b ), EFFECTIVE (T e ) HALF LIFEPharmaceuticals administered to living organismsdisappear from the biological system exponentiallyT b = The time needed for half of a pharmaceuticalto be excreted by a biological systemThe biological decay constant is λ b = 0.693 / T bPhysical Decay(T p ) and Biologic Excretion(T b ) resultin faster disappearance of a radiopharmaceuticalT e = The time needed for half the A o to disappearThe net or effective rate λ e = λ p + λ b, (λ = 0.693/t 1/2 )1/ T e = 1/ T p + 1/ T b and T e = (T p T b ) /(T p + T b )

ACTIVITY(A)= DISINTEGRATION RATE(D)==RADIOACTIVITY = DECAY RATEThe decay rate is proportionalto the total number of nuclei (N)dN/dt = λN = A = Dλ=decay constant ( sec -1 )Remaining radionuclides at any time (t) areN t = N o e -λt , e -λt = decay factorRadioactive decay is exponentialD t = D o e -λt or A t = A o e -λ t

UNITS OF RADIOACTIVITY1 curie (Ci) = Disintegration rate of 1 g of radium3.7 x 10 10 d/sec, mCi, µCi1 becquerel (Bq) = 1 d/sec, kBq, MBq, GBq, TBq1 mCi = 37 MBq (~40 MBq), 1 MBq = 27 µCiCARRIER FREE RADIONUCLIDE SAMPLESV/S MIXED SAMPLESSPECIFIC ACTIVITY: Activity per unit massCi/g, Bq/g( or per mole)

TRANSIENT EQUILIBRIUM

FISSION

FISSION

FISSION

CHAIN REACTION

ATOM BOMB

CONTROLLED CHAIN REACTION

NUCLEAR POWER PLANT

THREE MILE ISLAND NUCLEAR POWER PLANT

FUSION

FUSION REACTOR

FUSION NEW REACTOR

ELEMENTS OF NEW FUSION TECHNOLOGY

DETECTION AND MEASUREMENTOF RADIATION

PARTICLE ACCELERATOR

NUTRINO DETECTOR

MONITORING RADIOACTIVITY

GAS-FILLED RADIATION DETECTOR

QTPIE

RADIATION DETECTORS

GEIGER COUNTER

GEIGER-MULLER COUNTER

A DOSE CALIBRATOR

WELL COUNTER

GEOMETRIC EFICIENCY OF DETECTORS

LIQUID SCINTILLATION COUNTER

SCINTILLATION DETECTOR

SCINTILLATION COUNTER

SPECTRUM OF A 662keV GAMMA RAY OF 137 Cs

GAMMA-RAY SPECTRA

SPECTRUM OF 81keV gamma ray of 133 Xe

SPECTRUM OF 111 In

Spillover or Crosstalk

DEAD TIME IN PARALYZABLE ANDNONPARALYZABLE SYSTEMS

FULL WIDTH AT HALF MAXIMUM

THYROID PROBE

PERSONAL DOSIMETER

CRACKED CRYSTAL OF CAMERA

INTERFERENCE FROM AC Cs SOURCELymphoscintigraphy with the hybrid camera

QUALITY CONTROL IN NM

QUALITY CONTROL IN NM