ett seminar - isotopes in medicine

Post on 09-Apr-2018

218 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    1/71

    RADIOISOTOPESRADIOISOTOPESinin

    MEDICINE:MEDICINE:RequirementsRequirements ProductionProduction -- ApplicationApplication

    Gerd-Jrgen BEYERProf.Dr.habil.Cyclotron Unit,

    University Hospital of Geneva,Division of Nuclear Medicine

    Switzerland

    CERN, ETT Seminar

    March 04, 2002

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    2/71

    NUCLEAR MEDICINENUCLEAR MEDICINE

    HOW IT BEGANHOW IT BEGAN

    ! 1789 Klaproth Uran

    ! 1895 Conrad Rntgen X-Ray

    ! 1896 Henry Bequerel Radioactivity

    !

    1898 M.&P.Curie Po und Ra! 1923 G.Hevesy Tracer Principle

    ! 1932 Lawrence Cyclotron

    !

    1934 I.&F.Juliot-Curie Artif.Radiactivity! 1938 Hahn / Strassmann U-Fission

    L.Meitner

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    3/71

    W.C. RoentgenW.C. Roentgen

    discovers Xdiscovers X--raysrays 8. Nov.8. Nov. 18951895

    Radiograph of

    Mrs.Roentgens hand,the first x-ray imageever taken,22.Dec.1895, published inThe New York TimesJanuary 16, 1896

    W.C.Roentgens experiment

    in Wrzburg

    An early XXth century

    X-ray tube

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    4/71

    RADIOACTIVITYRADIOACTIVITY

    Antoine HenryAntoine Henry

    BecquerelBecquerel

    1896First image ofpotassium uranyldisulfate

    on 24 February 1896was the discovery ofnatural radioactivity

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    5/71

    RADIOACTIVITYRADIOACTIVITY

    Marie and Pierre Curiewith their daughter Irene

    Marie Curie

    1897 Becquerels friend, Pierre Curie, also Prof. of Physics in Paris, suggested to his young bride,Marie, that she study the phenomena discovered by H.Becquerel for her thesis. She found

    soon that some components of Uranium minerals were much more radioactive thanUranium itself. We shall call the mysterious rays radioactivity, she told to her husbandPierre, and the substances that produce the rays radioelements.

    1898 Pierre started to join Marie in the study of the mysterious rays. In July that year they reportedthe discovery ofPolonium (210Po) and in December they announced the discovery of the

    Radium (226Ra)

    1898 Polonium

    Radium

    1903 Nobel Prize

    together with Pierre

    1911 Nobel Prize

    alone

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    6/71

    THE TRACER PRINCIPLE 1923THE TRACER PRINCIPLE 1923

    G.V.HEVESY

    the father of Nuclear Medicine

    G.V.Hevesy:The Absorption and Translocation of

    Lead (ThB) by Plants [ThB =212

    Pb]Biochem.J. 17, 439 (1923)

    Measurements of the tracersradioactivity provided thousand fold

    increases in sensitivity and accuracy overexisting chemical assays. The foundationand basic rationale of much of Hevesyvisualized that a radioactive atom mightbe used as a representative tracer of

    stable atoms of the same element

    whenever and wherever it accompaniedthem in biological systems.

    1943 Nobel Prize Chemistry

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    7/71

    1934 Artificial RADIOACTIVITY1934 Artificial RADIOACTIVITYIrene and Pierre Joliot-Curie1934 Nature, February 10

    1935 Nobel PrizeOur latest experiments have shown a verystriking fact: when aluminum foil isirradiated on a polonium preparation, the

    emission of positrons does not ceaseimmediately when the active preparationis removed. The foil remains radioactiveand the emission of radiation decays

    exponentially as for an ordinary radio element.We observed the same phenomena with boronand magnesium.27Al (,n) 30P and 10B (,n) 13N

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    8/71

    INVENTION of the CYCLOTRONINVENTION of the CYCLOTRON

    Ernest O Lawrence and his

    First cyclotron 1932

    E.O Lawrenceand

    M.S.Livingston

    with the 27-inchcyclotron at

    Berkeley 1933,the first cyclotron

    that produced

    radioisotopes

    E.O.Lawrence and M.S. LivingstonThe production of high speed lightions without the use of high voltages,A milestone in the production of

    usable quantities of radionuclides.

    19321932

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    9/71

    The discovery of artificial radioactivity in combination with thecyclotron opened the door to the production of a variety of

    useful radio indicators . Practically any element could be bombardedin the cyclotron to generate radioactive isotopes.

    1935 Nature 136, 754 O.Chievitz and G.V.HevesyRadioactive indicators in the study of phosphorus metabolism in rats (32P)

    1937 Radiology 28, 178 J.G.Hamilton, R.S.Stone:The administration of radio-sodium (24Na)

    1938 Proc.Soc.Exp.Biol.Med. 38, 510 S.Hertz, A.Roberts, R.D.Evans

    Radioactive iodine (128I) Study of thyroid physiology1939 Proc.Soc.Exp.Biol.Med. 40, 694, J.H.Lawrence, K.G.Scott:

    Metabolism of phosphorus (32P) in normal and lymphomatous animals1940 Am.J.Physiol. 131, 135 J.G.Hamilton, M.H.Soley:

    Studies ofiodine metabolism by thyroid in situ1940 J.Biol.Chem. 134, 543 J.F.Volker, H.C.Hodge, H.J.Wilson

    The adsorption of fluoride (18F) by enamel, dentine, bone and hydroxyapatite1945 Am.J.Physiol. 145, 253 C.A.Tobias, J.H.Lawrence, F.Roughton

    The elimination of11C-Carbon monoxide from the human body

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    10/71

    Otto Hahn, 1944 Nobel Prize

    FISSION of UraniumFISSION of Uranium

    1938, 22 Dec.Naturwissenschaften 1, (1939) 1O.Hahn und F.Stramannber den Nachweis und das Verhalten der beider Bestrahlung des Urans mittels Neutronenentstehenden Erdalkalimetalle

    Lise Meitner and O.R Frisch described theExplanation and defined the terminus FISSION

    Als Chemiker mten wir statt

    Ra, Ac und Th die Symbole Ba, La und Ceeinsetzen. Als der Physik in gewisser Weisenahestehende Kernchemiker knnen wiruns zu diesem, allen bisherigen Erfahrungender Kernphysik widersprechenden Sprungnoch nicht entschlieen. Es knnten dochvielleicht eine Reihe seltsamer Zuflleunsere Ergebnisse vorgetuscht haben.

    Niels Bor (Jan.1939)Mein Gott, wie haben wir das

    Nur so lange bersehen knnenLaboratory table of Otto Hahn

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    11/71

    FISSION of UraniumFISSION of Uranium235U + n = [236U] 140Ba + 94 Kr + 2 n + + Energy

    1942 Dec.2, first graphite miler in Chicago

    1946 Dec.25, first graphite miler in Moscow

    Note: first A-Bomb 1945/1949, first atomic E-power station 1954

    Enrico Fermi

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    12/71

    10 MW swimming pool reactor, Geesthacht (D)

    Foto: G.Beyer, 1973

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    13/71

    1946, June 14Nuclear Medicines modern era began

    Availability of Radioactive Isotopes,Announcement from Headquarters, Manhatten Project, Washington D.C.:

    Production of tracer and therapeutic radioisotopes has been

    heralded as one of the greatest peacetime contributionsof the uranium chain-pile. This use of the uranium pile

    will unquestionably be rich in scientific, medical,

    and technological application.

    On 1.Aug.1946 the Atomic Energy Actpassed the congress,

    releasing radioisotopes from military control.

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    14/71

    ISOTOPES IN MEDICINEISOTOPES IN MEDICINE

    THERAPYDIAGNOSIS

    internal externalin vitro in vivo

    systemic sources tele radio14C3H125I

    others

    99Mo-99mTc

    201Tl123I

    111In

    67Ga81Rb-81mKr

    others

    + emittersfor PET

    18F, 11C,13N,15O86Y, 124I

    68Ge-68Ga82

    Sr-82

    Rb

    131I,90Y153Sm,186Re188W-188Re

    166

    Ho,

    177

    Lu,others

    -emitters:225Ac-213Bi

    211At, 223Ra149Tb

    e--emitters:125

    I

    sealed sources192Ir,182Ta, 137Csmany others

    needles for

    brachytherapy:103Pd, 125Imany others

    stants32P and others

    seeds90Sr or 90Y, others

    applicators137Cs, others

    60Co

    gamma

    knife

    137Csblood

    cell

    irradi-ation

    G.J.BEYER, HUG Geneva, 2000

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    15/71

    ISOTOPESISOTOPES inin

    MEDICINEMEDICINEApplication Requirement Isotope

    11C,13N, 15O,

    18F

    +-decay mode

    biogenic elements

    T = short

    DIAGNOSIS

    in vivo

    PET

    99mTc,123I, 111In,

    201Tl,

    single photonsno particles

    biogenic behavior

    T

    = moderate

    DIAGNOSISIn vivo

    SPECT

    3H, 14C125I

    T = long

    biogenic behavior

    DIAGNOSISin vitro

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    16/71

    Rosalyn S.YALOW S.A.BERSONNobel Prize 1977

    Introduced the radio immuno assay (RIA)

    (assay for insulin based on the principle of competitive binding by antibodyof natural and radioactive labeled hormone)

    Diagnostic in vitro RIA

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    17/71

    124Xe (n,) 125Xe 125IEC

    = 22 b

    = 106 b

    57 sec

    16.8 h

    125Xe

    125

    I

    ( n, )

    60.14 d

    = 894 b

    126I (13.6 d)

    35.5 keV

    Summe peaks

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    18/71

    ISOTOPESISOTOPESinin

    MEDICINEMEDICINEApplication Requirement Isotope

    11C,13N, 15O,

    18

    F

    +-decay mode

    biogenic elements

    T = short

    DIAGNOSIS

    in vivo

    PET

    99mTc,123I, 111In,

    201Tl,

    single photons

    no particles

    biogenic behavior

    T

    = moderate

    DIAGNOSISIn vivo

    SPECT

    3H, 14C125I

    T = long

    biogenic behavior

    DIAGNOSISIn vitro

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    19/71

    NUCLEAR MEDICINENUCLEAR MEDICINE ==

    in vivo APPLICATION ofin vivo APPLICATION of RADIOTRACERSRADIOTRACERS

    1923 First tracer study with 210Pb/210Bi G.Hevesy

    1925 214Bi arm-to-arm circulation time, H.Blumgart

    1935 32P renewal of mineral constituents of bone, O.Chieivitz & G.Hevesy1937 dynamics of sodium transport in vivo, J.G.Hamilton

    1937 128I, thyroid physiology, R.Hertzs, A.Roberts, R.Evans

    1938 131I discovered by G.T.Seeborg, 1939 first diagnostic use J.G.Hamilton et al.

    1947 131I Fluorescine, 1950 131I HSA, 1955 131I-rose bengale & hippurane,

    1957 99Mo-99mTc generator (1960 first sale), 133Xe for lung ventilation

    1969 67Ga accumulation in cancer, C.L.Edwards

    1970 Instant KITs for99m

    Tc1973 201Tl and this time 123I, 111In, many other isotopes and tracer compounds

    1977 first 18FDG PET scan

    11 million individuals receive every year a radiotracer for diagnosis

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    20/71

    J.G.Hamilton, M.H.Soley:

    Studies ofiodine

    metabolism by

    thyroid in situ1940, Am.J.Physiol. 131, 135

    Photo published 1942

    Kidney Isotope Nephrogram

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    21/71

    signalsx+, x-, y+, y-

    windowlight gide

    NaI-Detector

    collimator

    PM tubes

    Pb shielding

    electronics

    GAMMA CAMERA

    H.O.ANGER

    1958

    SCANNER

    B.CASSEN

    Planar scintigram

    Scan Thyroid normal

    Pre-amplifier

    PM-tube

    Pb-shieldingNaI-Detector

    Collimator

    Object

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    22/71

    SPECT

    Single Photon Emission Computed Tomography

    1984 99mTc DMPE

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    23/71

    Modern SPET

    Cameras

    (GE Medical Systems)

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    24/71

    NUCLEAR MEDICINE 2000

    DIAGNOSIS THERAPIE

    SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY)* increase of diagnostic value* new radiopharmaceuticals

    * dedicated instrumentation & quantification

    PET AS RESEARCH TOOL* Molecular in vivo biochemistry* Gene expression* Clinical research

    PET AS CLINICAL TOOL* Oncology

    Reimbursement of FDG-studies* Neurology* Cardiology

    Multi-modality Imaging* combined SPECT-PET

    (image of the year at the 46.SNM)* Function and morphology

    (PET - CT or SPECT - CT)

    NEW APPROACHES INRADIONUCLIDE THERAPY

    * bio-selective antibodies

    (mab = monoclonal antibodies)* bio-specific Peptides

    (Octreotides, others)* gene therapy* free chelators like EDTMP* labelled particles (microspheres, colloids)

    * labelled macromoleculesNEW RADIONUCLIDES

    for THERAPY* - - emitters* - emitters (213Bi, 149Tb)

    -THERAPY & AUGER THERAPY

    PET FOR IN-VIVO DOSIMETRY

    * metallic positron emitters* labelled drugs

    * dose localizationG.BEYER (HUG Geneva, 2000)

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    25/71

    ISOTOPES IN MEDICINEISOTOPES IN MEDICINE

    THERAPYDIAGNOSIS

    internal externalin vitro in vivo

    systemic sources tele radio14C3H125I

    others

    99Mo-99mTc

    201Tl123I

    111In

    67Ga81Rb-81mKr

    others

    + emitters

    for PET18F, 11C,13N,15O

    86Y, 124I68Ge-68Ga82

    Sr-82

    Rb

    131I,90Y153Sm,186Re188W-188Re

    166Ho,177Lu,others

    -emitters:225Ac-213Bi

    211At, 223Ra149Tb

    e--emitters:125

    I

    sealed sources192Ir,182Ta, 137Csmany others

    needles for

    brachytherapy:103Pd, 125Imany others

    stants32P and others

    seeds90Sr or 90Y, others

    applicators137Cs, others

    60Co

    gamma

    knife

    137Csblood

    cell

    irradi-ation

    G.J.BEYER, HUG Geneva, 2002

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    26/71

    141 keV photons - the strength of99mTc

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    27/71

    99mTcO4-

    0.9 % NaCl solution +

    KITs

    many different99mTc-tracerfor

    imaging of manydifferent

    organ and tissue

    functions

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    28/71

    Ventilation study

    LUNG Function

    Perfusion Study

    99mTc

    TRACERExamples

    HEARTPerfusion

    BONEMetabolicactivity

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    29/71

    99

    Mo: PRODUCTION ROUTES98Mo ( n, ) 99Mo

    = 0.130 b1 g 98 Mo, nth = 1 * 10

    13 cm-2s-1

    8 GBq 99Mo/g 98Mo (low specific activity)

    235U ( n; f ) 99Mo= 586 b

    99Mo - fission yield = 6.15 %

    1 g 235 U, nth = 1 * 1013 cm-2

    914 GBq99

    Mo/mg Mo (high specific activity)

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    30/71

    ISOTOPE PRODUCTION

    REACTORneutrons

    High energy proton

    induced reactions

    CYCLOTRONcharged particles

    Neutron rich

    ISOTOPES

    Proton rich

    ISOTOPES

    - - emitter

    EC, , + - emitter

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    31/71

    REACTOR: Problems of RI Production

    ! Radiation dose targets: elements, oxides, carbonates only, no organiccompounds, material requirements for capsules

    !

    Temperatureresearch reactors usually 60 oC, reactors in powerstations useful for special activations only (60Co)

    ! Heat production nuclear reaction energy heats up the targets, fissionenergy, large target masses low heat transfer

    ! Burn out losses of product and generation of impurities,significant, when > 1000 b

    ! N-depression must be considered when > 10 b, lowers yield

    ! Side reactions impurities with high , other reactions

    ! Irradiation time can be long, that is an advantage

    ! Targets large and many different, is an advantage

    ! Availability number of reactors decreases - main problem

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    32/71

    Problems of medical RI Production with

    CYCLOTRONS

    Short range of the particle beamRange: 30 MeV p about 1 mm15 MeV d about 0.3 mm

    30 MeV a about 0.1 mm

    small target - high thermic energy deposition!

    Small cross sectionsLow productivity

    Limited and expensive target materialenriched isotopes

    VacuumTarget window problems, sensitive target material

    Single target one isotope

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    33/71

    r+b-b 0

    p, d, He, Hi

    E

    Particle Beam EnergyParticle Beam Energy

    at b strong nuclear force

    only one particle out of 104107 reacts in reality

    full particle beam is stopped inside the target material

    the whole particle energy is transformed into thermicenergy (heat)

    Ep = 30 MeV,

    Ip = 100 A

    Eth = 3 kW

    Area = 1 cm

    Range = 1 mm

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    34/71

    Zn on Cu Backing

    14 MeV d, 50 AU-120 Cyclotron Rossendorf

    1979

    photo

    autoradiogram

    autoradiogram

    1 water in

    2 water out3 openings

    4 winding A8

    BEAM

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    35/71

    Target systemfor irradiation of

    Sensitive target materials

    inside thevacuum chamber of a

    cyclotroncyclotron

    Cu3AS-alloy as

    target for the77

    Brproduction

    FZ Jlich, 1983

    Qaim & Stcklin

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    36/71

    IBA Cyclone 18/9, Cyclotron in Geneva

    9 MeV Deuteron beam spoton the Havar Window foil

    of the Ne(F2) [18F]F2 target

    inside the target chamber outside

    Ed = 9 MeV, Id = 18 A, area few mm2

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    37/71

    Excitation function for proton induced reactions

    10

    100

    1000

    10000

    0 5 10 15 20 25 30 35 40 45 50

    energy in MeV

    crossse

    ctioninmb

    123Te(p;n)123I

    124Te(p;2n)124I

    75As(p;3n)73Se

    75As (p;4n) 72Se

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    38/71

    123-IODINE PRODUCTION ROUTES

    123 Cs 123Xe 123I5.9 min 2.08 h

    EC/+ EC

    124I = 1 %125I < 1 %125 I < 10-3 %

    22 28 MeV75 MeV p20 30 MeV p

    124Te (p,2n)127I (p,5n)124Xe (p,2n)

    1985Karlsruhe, Canada

    1980 PSIWrenlingen

    1975many places

    ALTERNATIVES:local 123 I production using PET cyclotrons

    123Te (p,n) 123 I

    15 MeV p, 150 MBq/Ah

    Fast, easy, reliable, clean product, suitable for direct labeling

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    39/71

    irradiated Tl- target

    dissolution in 6M HNO3Fe3+ carrier

    hydroxide precipitation

    Fe(OH)3 collects201Pb

    dissolution in 6 M HNO3hydroxide precipitation

    dissolution in 6M HNO3Fe(OH)3 collects

    201Pb

    DOWEX 1x8 column

    elution with 6 M HCl

    decay of 201Pb,

    formation of201

    Tldecay period 30 h

    reduction of Tl3+ to Tl1+

    elution with 3 M HCl201

    Tl

    Target: 1 3 g enriched 203Tl

    irradiation with 30 MeV protonscomplete separation of Tl from 201Pb

    decay of 201Pb into 201Tl

    separation of

    201

    Tl from

    201

    Pb

    TlTl

    Tl

    Fe

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    40/71

    Nuclear MedicineNuclear Medicine InstrumentationInstrumentation

    2 D and 3 D

    dyn. & quantitative

    2 D 3 D

    dynamic dynamic

    1 D 2 D

    dynamic static

    multi-ring systemsBlock detectors BGO

    PET

    NaI + many PMssingle head 1-3 heads

    -Camera SPECT

    single detectorGM / NaI -PM NaI-PM

    Probe Scanner

    combined

    with / without septa

    DETECTORare

    place sensitive

    stationary moving

    multi-hole collimators

    point sensitive

    stationary moving

    Point collimator

    67GaCIT 99mTc DMPE

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    41/71

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    42/71

    ISOTOPESISOTOPESfor Tracerfor Tracer SynthesisSynthesis

    [15O]H2OH2O14N (d,n) 15O2 min15O

    unlimitedN214N (p,) 11C20 min11C

    ProductTargetReactionT 1/2ISOTOPE

    [18F]FDG

    [18F]FDOPA

    [18O]H2O

    20Ne

    18O (p,n) 18F20Ne (d, ) 18F

    110 min18F

    [13N]NH3H2O16O (p,) 13N10 min13N

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    43/71

    July.2000

    IBA CYCLONE 18/9

    Cyclotron Unit Geneva

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    44/71

    HOT LAB

    HotHot CellsCells

    Cyclotron Unit Geneva

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    45/71

    FDG-PET Dementia - Alzheimers

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    46/71

    PET inPET in oncologyoncology

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    47/71

    PET inPET in oncologyoncology

    FDG-PET Melanoma therapy control

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    48/71

    FDG-PET Melanoma therapy control

    before

    after

    Fused ImageFused Image TomographyTomography

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    49/71

    Fused ImageFused Image TomographyTomography

    Fused image viewer

    Radiology Nuclear Medicine

    Biopsy

    Therapyresponse

    Pre

    Post

    IMRT

    PET/CTscanner

    Diagnosisand

    Staging

    Surgery OncologyD.Townsend & T.Beyer, Pittsburg

    Image of the Year 1999, 46.SNM Los Angeles

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    50/71

    Image of the Year 1999, 46.SNM Los Angeles

    D.Townsend, T.Beyer

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    51/71

    STATUSSTATUS PETPET 20022002

    ww USA D CH

    Cyclotrons 285 115 20 2

    Scanners 700 375 85 5

    Market Shares:

    Cyclotrons: CTI/TCC 65 % GE/Scanditr. 25 %

    Scanners: CTI/Siemens 55-60% GE 20 %

    ADAC/UGM 16 %

    NUCLEAR MEDICINE 2000

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    52/71

    NUCLEAR MEDICINE 2000DIAGNOSIS THERAPIE

    SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY)* increase of diagnostic value* new radiopharmaceuticals* dedicated instrumentation & quantification

    PET AS RESEARCH TOOL* Molecular in vivo biochemistry* Gene expression* Clinical research

    PET AS CLINICAL TOOL* Oncology

    Reimbursement of FDG-studies* Neurology* Cardiology

    Multi-modality Imaging* combined SPECT-PET

    (image of the year at the 46.SNM)* Function and morphology

    (PET - CT or SPECT - CT)

    NEW APPROACHES INRADIONUCLIDE THERAPY

    * bio-selective antibodies

    (mab = monoclonal antibodies)* bio-specific Peptides(Octreotides, others)

    * gene therapy* free chelators like EDTMP* labelled particles (microspheres, colloids)* labelled macromolecules

    NEW RADIONUCLIDESfor THERAPY

    * - - emitters* - emitters (213Bi, 149Tb)

    -THERAPY & AUGER THERAPY

    PET FOR IN-VIVO DOSIMETRY

    * metallic positron emitters* labelled drugs

    * dose localization G.BEYER (HUG Geneva, 2000)

    ISOTOPES IN MEDICINEISOTOPES IN MEDICINE

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    53/71

    SO O S C

    THERAPYDIAGNOSIS

    internal externalin vitro in vivo

    systemic sources tele radio14C

    3H125I

    others

    99Mo-99mTc

    201Tl123I

    111In67

    Ga81Rb-81mKrothers

    + emitters

    for PET18F, 11C,13N,15O

    86Y, 124I68Ge-68Ga82Sr-82Rb

    131I,90Y153Sm,186Re188W-188Re

    166Ho,177Lu,

    others

    -emitters:225Ac-213Bi

    211

    At,223

    Ra149Tb

    e--emitters:125I

    sealed sources192Ir,182Ta, 137Csmany others

    needles forbrachytherapy:103Pd, 125I

    many others

    stants32P and others

    seeds90Sr or 90Y, others

    applicators137Cs, others

    60Co

    gammaknife

    137Csblood

    cellirradi-

    ation

    G.J.BEYER, HUG Geneva, 2002

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    54/71

    CANCERCANCERAbout 1 000 000 new cancer cases per year in EU

    58 % local disease, 42 % generalized45 % cured (5 year survival)

    22 % surgery alone

    12 % radiation therapy6 % combination surgery + radiation5 % chemo-therapy

    just beginning of systemic radionuclide therapy

    HOW: expose cancer cells or cancer tissuewith sufficient radiation doses?

    Cancer cases 1997

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    55/71

    0

    10000

    20000

    30000

    40000

    50000

    60000

    Mund / Rachen

    Verdauungsorgane

    Atmungsorgane

    Knochen

    Bindegewebe

    Haut Melanom

    Brustdrse

    W. Geschlechtsorgane

    Prostata

    Hoden

    Penis

    Harnblase

    Niere

    Nervensystem

    Schilddrse

    Non-Hodgkin-L.

    Cancer

    ProbabilityinG

    erman

    (sourceRKI)M

    164

    F

    172

    ISOTOPES i ThISOTOPES in Therapy

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    56/71

    ISOTOPES in Therapy =ISOTOPES in Therapy =surgery with radiationsurgery with radiation

    molecularsurgery

    cell surgerytissue surgery

    in vivo

    tissue surgery

    ex vivo

    futureleukemiaRITRadio-immuno therapy

    headcancer

    application

    1 m30 80 mabout 1 cmfull body

    penetrationrange

    125I165Er

    Ee few eV

    212, 213 Bi,211At, 149Tb,

    223, 224Ra

    E 48 MeV

    131I, 90Y,153Sm,166Ho,

    others

    E 1 3 MeV

    60Co

    E> 1 MeV

    ISOTOPE

    Auger

    Knife-Knife-Knife

    Gamma

    Knife

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    57/71

    FDG-PET

    Astrocytoma

    after treatmentwith the

    Gamma KnifeRadiation necrosis

    in left parietal lobe

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    58/71

    RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPY

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    59/71

    RIT== RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPY

    oror RRADIOADIOIIMMUNOMMUNO TTHERAPYHERAPY

    oror systemic radionuclide therapysystemic radionuclide therapy

    1936 32P against leukemia, J.H.Lawrence

    1939 89Sr uptake in bone metastases, C.Pecher1946 131I treatment of thyroid cancer, S.M.Seilin et al.

    1963 Radioactive colloides, B.Ansell et al.1976 89Sr against pain from bone metastases, N.Firusian

    1978 Radiolabelled mab, D.Goldenberg1982 Treatment with 131I labelled mab, S.Larson et al.

    1990 Somatostatine receptor binding tracers, E.Krenning1993 89Sr, FDA approval

    2000 FDA approval of131I-CD20 against Lymphoma ?

    Development of therpeuticals is delayed

    -

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    60/71

    130

    Te (n,)131

    Te131

    I

    Simplif ied scheme

    for131

    I-production viathermal neutron irradiation

    of natural TeO2

    = 0.02 b

    = 0.27 b

    IT22 %

    182 keV30 h

    25 min

    78 %22 %

    131I

    8.04 d

    -

    spectrum 131I

    Emax

    131I Production Technology

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    61/71

    gy

    Hot Cell Facility

    Target Processing

    Iodine Trapping

    RITRIT == RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPY

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    62/71

    RIT

    oror RRADIOADIOIIMMUNOMMUNO TTHERAPYHERAPY

    0.1

    0.147

    0.269

    0.7

    4.2

    Range[mm] [keV][MeV]

    softno9.4 d0.3169Er

    interesting15980.4 h0.4/0.647Sc

    Interesting18561.9 h0.4/0.667Cu

    Not easy113/2086.7 d0.5177Lu

    mostcommon

    (364keV)8.04 d0.8131I

    Easy, carrier103 keV46.8 h0.8153Sm

    Carrier13790.6 h1.1186Re

    Palliationonly

    no50.5 d1.589Sr

    difficult(81 keV)26.8 h1.9166Ho

    Difficult,generator

    155 keV17 h2.1188Re

    Easy

    available

    no64.1 h2.390Y

    commentphotonsT EmaxNuclide

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    63/71

    H.Mcke, Basle

    ALPHA EMITTERS FOR THERAPY

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    64/71

    225Ac 10 d 233U decay chain 226Ra (p,2n) 225Ac229Th (-decay) 225Ra

    224Ra 3.66 d 233U decay chain228Th (-decay) 224Ra

    223Ra 11.4 227Ac decay chain 226Ra (n,) 227Ac227Th (-decay) 223Ra

    213Bi 45.6 m 225Ac decay chain AcBi generator212Bi 60 m 224Ra decay chain RaBi/Pb generator

    211At 7.2 h 209Bi (,2n) 211At

    149Tb 4.1 h Ta (p,spall)

    152Gd (p,4n) 149Tb

    C ll b

    Principle of Radioimmunio Therapy

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    65/71

    Protein strand in cancer cells(CD20 antigens of B cells)

    Cell membrane

    MoAb (Rituximab)specific to

    CD20 antigensof B cells

    149TbDAUDI cells

    Linker(CHX-A-DTPA)Proteins in healthy cells

    Plasma

    149Tb134Ce/La 140Nd/Pr

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    66/71

    138

    Nd/Pr152

    Tb

    142SmEDTMP in vivo study

    142Sm/Pm

    Positron emitting radio-lanthanides for individual in vivo dosimetry

    PET phantom studies

    The GenevaThe Geneva PETPET andand CERNCERN

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    67/71

    142-SmEDTMP, 60 min p.i.

    CERN: the world largestacceleartor complex for fundamentalparticle physics research

    ISOLDE: the world leading on lineisotope separation facility and provides

    - universal access practically to all

    radionuclides- in unprecendented purity,

    very useful for biomedical research,

    integrated into theGeneva PET Program

    (in vivo dosimetry based on PET)

    3D whole3D whole--body PETbody PET

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    68/71

    yy

    25 year-old male with Melanoma,71 kg, 178 cm, 625 MBq FDG, 45 min p.i.

    50 year-old male with colon CA91 kg, 183 cm, 720 MBq FDG, 162 min p.i.

    ECAT HR+

    Data courtesy of

    Kettering Memorial Hospital, Kettering, USA

    Data courtesy of

    NC PET Imaging Center, Sacramento, USA

    ECAT ACCEL

    Emission scan time: 54 min

    Transmission scan time: 18 minEmission scan time: 27 min

    Transmission scan time: 18 min

    RADIOISOTOPES in MEDICINE:Trends Market R&D (1)

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    69/71

    Trends Market R&D (1)

    Resume from the

    Medical Isotope Workshop, Dalles, (Texas) May 2-3, 1998

    US only

    Status: Health Care totally: around 1 * 1012 US-$(1998) Surgery 50 100 * 109 US-$

    Radiation 1 - 5 * 109 US-$

    Roy BROWN Nucl. Med.1998 10.5 * 106 studies

    Richard REBA Isotope 1996 48 * 106 US-$demand for 2001 62 * 106 US-$

    therapy only 2020 6000 * 106 US-$

    RADIOISOTOPES in MEDICINE:Trends Market R&D (2)

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    70/71

    Trends Market R&D (2)

    Market : Brachytherapy (Prostate) 1998 100 * 106 US-$Bill EHMIG increasing 125I, 103Pd seeds

    huge market (14 cyclotrons only for103

    Pd)trend: change from palliation to cure !

    Other sources: lymphome therapy Curie Therapy131I-LYM-1 mab, US only 100 * 106 US-$ /y(today 131I -CD-20-mab up to 0.8 Ci dose/patient)

    Henry WAGNER: full radiotracer development program,

    not just radionuclide development a national governmental facility provides theinfrastructure, industry provides the distributionnetwork

    HOW ?

    TRENDS - OUTLOOK

  • 8/8/2019 ETT Seminar - Isotopes in Medicine

    71/71

    80 % of worldwide produced radioisotopesare used in medicine

    The demand of selected radioisotopes is still growing.

    Therapy with radionuclides has a great potential

    for the near future:

    therpeutic radionuclides

    sources for brachytherapy

    PET has clinical relevance.

    Distribution of PET-tracers is just at the beginning.