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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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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
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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
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HOT LAB
HotHot CellsCells
Cyclotron Unit Geneva
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FDG-PET Dementia - Alzheimers
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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)
ISOTOPES IN MEDICINEISOTOPES IN MEDICINE
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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
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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
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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.