ETT Seminar - Isotopes in Medicine

8/8/2019 ETT Seminar - Isotopes in Medicine

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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


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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


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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


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RADIOACTIVITYRADIOACTIVITY

Antoine HenryAntoine Henry

BecquerelBecquerel

1896First image ofpotassium uranyldisulfate

on 24 February 1896was the discovery ofnatural radioactivity


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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


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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


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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


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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


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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


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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


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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


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10 MW swimming pool reactor, Geesthacht (D)

Foto: G.Beyer, 1973


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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.


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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


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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


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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


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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


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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


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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


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

Studies ofiodine

metabolism by

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

Photo published 1942

Kidney Isotope Nephrogram


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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


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SPECT

Single Photon Emission Computed Tomography

1984 99mTc DMPE


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Modern SPET

Cameras

(GE Medical Systems)


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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)


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THERAPYDIAGNOSIS


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


211At, 223Ra149Tb

e--emitters:125

I


needles for

brachytherapy:103Pd, 125Imany others




60Co

gamma

knife

137Csblood

cell

irradi-ation



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141 keV photons - the strength of99mTc


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99mTcO4-

0.9 % NaCl solution +

KITs

many different99mTc-tracerfor

imaging of manydifferent

organ and tissue

functions


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Ventilation study

LUNG Function

Perfusion Study

99mTc

TRACERExamples

HEARTPerfusion

BONEMetabolicactivity


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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)


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ISOTOPE PRODUCTION

REACTORneutrons

High energy proton

induced reactions

CYCLOTRONcharged particles

Neutron rich

ISOTOPES

Proton rich

ISOTOPES

- - emitter

EC, , + - emitter


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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July.2000

IBA CYCLONE 18/9

Cyclotron Unit Geneva


44/71

HOT LAB

HotHot CellsCells

Cyclotron Unit Geneva


45/71

FDG-PET Dementia - Alzheimers


46/71

PET inPET in oncologyoncology


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PET inPET in oncologyoncology

FDG-PET Melanoma therapy control


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FDG-PET Melanoma therapy control

before

after

Fused ImageFused Image TomographyTomography


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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


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Image of the Year 1999, 46.SNM Los Angeles

D.Townsend, T.Beyer


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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


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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)



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SO O S C

THERAPYDIAGNOSIS


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


211

At,223

Ra149Tb

e--emitters:125I


needles forbrachytherapy:103Pd, 125I

many others




60Co

gammaknife

137Csblood

cellirradi-

ation



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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


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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


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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


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FDG-PET

Astrocytoma

after treatmentwith the

Gamma KnifeRadiation necrosis

in left parietal lobe


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RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPY


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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

-


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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


61/71

gy

Hot Cell Facility

Target Processing

Iodine Trapping

RITRIT == RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPY


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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


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H.Mcke, Basle

ALPHA EMITTERS FOR THERAPY


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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


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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


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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


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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


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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)


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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)


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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


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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.

Documents

ETT Seminar - Isotopes in Medicine