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RADIOISOTOPES

in
MEDICINE:
Requirements – Production - Application
Gerd-Jürgen BEYER
Prof.Dr.habil.
Cyclotron Unit,
University Hospital of Geneva,
Division of Nuclear Medicine
Switzerland

CERN, ETT Seminar


March 04, 2002
NUCLEAR MEDICINE –
HOW IT BEGAN
! 1789 Klaproth Uran
! 1895 Conrad Röntgen 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
W.C. Roentgen
8. Nov. 1895
discovers X-rays

W.C.Roentgens experiment
in Würzburg

Radiograph of
Mrs.Roentgens hand,
the first x-ray image
ever taken,
An early XXth century 22.Dec.1895, published in
The New York Times
X-ray tube January 16, 1896
1896 RADIOACTIVITY
First image of
potassium uranyldisulfate
on 24 February 1896
was the discovery of
natural radioactivity

Antoine Henry Becquerel


RADIOACTIVITY
1898 Polonium
Radium

1903 Nobel Prize


together with Pierre
1911 Nobel Prize
alone
Marie and Pierre Curie
with 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 than
Uranium itself. “We shall call the mysterious rays ‘radioactivity’,” she told to her husband
Pierre, 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 reported
the discovery of Polonium (210Po) and in December they announced the discovery of the
Radium (226Ra)
THE TRACER PRINCIPLE 1923
G.V.Hevesy:
The Absorption and Translocation of
Lead (ThB) by Plants [ThB = 212Pb]
Biochem.J. 17, 439 (1923)

Measurements of the tracer’s


radioactivity provided thousand fold
increases in sensitivity and accuracy over
existing chemical assays. The foundation
and basic rationale of much of Hevesy
visualized that a radioactive atom might
be used as a “representative” tracer of
stable atoms of the same element
whenever and wherever it accompanied
them in biological systems.
1943 Nobel Prize Chemistry
G.V.HEVESY
the father of Nuclear Medicine
1934 Artificial RADIOACTIVITY
Irene and Pierre Joliot-Curie
1934 Nature, February 10
1935 Nobel Prize
“Our latest experiments have shown a very
striking fact: when aluminum foil is
irradiated on a polonium preparation, the
emission of positrons does not cease
immediately when the active preparation
is removed. The foil remains radioactive
and the emission of radiation decays
exponentially as for an ordinary radio element.
We observed the same phenomena with boron
and magnesium.”
27Al α,n) 30P and
(α 10B α,n) 13N

INVENTION of the CYCLOTRON
1932
E.O.Lawrence and M.S. Livingston
“The production of high speed light
ions without the use of high voltages”,
A milestone in the production of
usable quantities of radionuclides.

E.O Lawrence
and
M.S.Livingston
with the 27-inch
cyclotron at
Berkeley 1933,
the first cyclotron
Ernest O Lawrence and his that produced
First cyclotron 1932 radioisotopes
The discovery of artificial radioactivity in combination with the
cyclotron opened the door to the production of a variety of
useful radio indicators . Practically any element could be bombarded
in the cyclotron to generate radioactive isotopes.

1935 Nature 136, 754 O.Chievitz and G.V.Hevesy


Radioactive 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 physiology
1939 Proc.Soc.Exp.Biol.Med. 40, 694, J.H.Lawrence, K.G.Scott:
Metabolism of phosphorus (32P) in normal and lymphomatous animals
1940 Am.J.Physiol. 131, 135 J.G.Hamilton, M.H.Soley:
Studies of iodine metabolism by thyroid in situ
1940 J.Biol.Chem. 134, 543 J.F.Volker, H.C.Hodge, H.J.Wilson
The adsorption of fluoride (18F) by enamel, dentine, bone and hydroxyapatite
1945 Am.J.Physiol. 145, 253 C.A.Tobias, J.H.Lawrence, F.Roughton
The elimination of 11C-Carbon monoxide from the human body
FISSION of Uranium
1938, 22 Dec.
Naturwissenschaften 1, (1939) 1
O.Hahn und F.Straßmann
Über den Nachweis und das Verhalten der bei
der Bestrahlung des Urans mittels Neutronen
Otto Hahn, 1944 Nobel Prize entstehenden Erdalkalimetalle
Als Chemiker müßten wir … statt
Ra, Ac und Th die Symbole Ba, La und Ce
Lise Meitner and O.R Frisch described the
einsetzen. Als der Physik in gewisser Weise Explanation and defined the terminus “FISSION”
nahestehende Kernchemiker können wir
uns zu diesem, allen bisherigen Erfahrungen
der Kernphysik widersprechenden Sprung
noch nicht entschließen. Es könnten doch
vielleicht eine Reihe seltsamer Zufälle
unsere Ergebnisse vorgetäuscht haben.

Niels Bor (Jan.1939)


Mein Gott, wie haben wir das
Nur so lange übersehen können
Laboratory table of Otto Hahn
FISSION of Uranium
235U + n = [236U] 140Ba + 94 Kr + 2 n + γ + Energy
1942 Dec.2, first graphite miler in Chicago

Enrico Fermi
1946 Dec.25, first graphite miler in Moscow
Note: first A-Bomb 1945/1949, first atomic E-power station 1954
Foto: G.Beyer, 1973

10 MW swimming pool reactor, Geesthacht (D)


1946, June 14
Nuclear Medicine’s 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 contributions
of 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 Act


passed the congress,
releasing radioisotopes from military control.
ISOTOPES IN MEDICINE
DIAGNOSIS THERAPY
in vitro in vivo internal external

99
14C Mo-99mTc systemic sources tele radio

3H 131I,90Y sealed sources


201Tl 192Ir,182Ta, 137Cs 60Co
125I 153Sm,186Re
123I many others
others 188W-188Re
111In needles for gamma
166Ho,177Lu,
67Ga brachytherapy: knife
81Rb-81mKr
others 103Pd, 125I

α-emitters:
137Cs
many others
others stants blood
225Ac-213Bi cell
32P
ß+ emitters 211At, 223Ra
and others
irradi-
for PET seeds ation
18F, 11C,13N,15O 149Tb 90Sr or 90Y, others
86Y, 124I
68Ge-68Ga e--emitters: applicators
137Cs, others
82Sr-82Rb 125I

G.J.BEYER, HUG Geneva, 2000


ISOTOPES in MEDICINE
Application Requirement Isotope

DIAGNOSIS T½ = long 3H, 14C


in vitro
biogenic behavior 125I

DIAGNOSIS single photons 99mTc,


In vivo no particles
123I, 111In,
SPECT biogenic behavior
201Tl,
T½ = moderate
DIAGNOSIS ß+-decay mode 11C,

in vivo biogenic elements 13N, 15O,

PET T½ = short 18F


Diagnostic in vitro RIA

Rosalyn S.YALOW S.A.BERSON


Nobel Prize 1977
Introduced the radio immuno assay (RIA)
(assay for insulin based on the principle of competitive binding by antibody
of natural and radioactive labeled hormone)
EC
124Xe (n,γγ) 125Xe 125I

σ = 22 b 57 sec
35.5 keV
16.8 h
σ = 106 b

125Xe
Summe peaks

60.14 d

( n, γ)
125I 126I (13.6 d)
σ = 894 b
ISOTOPES in MEDICINE
Application Requirement Isotope

DIAGNOSIS T½ = long 3H, 14C


In vitro
biogenic behavior 125I

DIAGNOSIS single photons 99mTc,


In vivo no particles
123I, 111In,
SPECT biogenic behavior
201Tl,
T½ = moderate
DIAGNOSIS ß+-decay mode 11C,

in vivo biogenic elements 13N, 15O,

PET T½ = short 18F


NUCLEAR MEDICINE =
in vivo APPLICATION of RADIOTRACERS
1923 First tracer study with 210 Pb/210 Bi G.Hevesy
214
1925 Bi arm-to-arm circulation time, H.Blumgart
32
1935 P renewal of mineral constituents of bone, O.Chieivitz & G.Hevesy
1937 dynamics of sodium transport in vivo, J.G.Hamilton
128
1937 I, thyroid physiology, R.Hertzs, A.Roberts, R.Evans
131
1938 I discovered by G.T.Seeborg, 1939 first diagnostic use J.G.Hamilton et al.
131
1947 I –Fluorescine, 1950 131 I –HSA, 1955 131 I-rose bengale & hippurane, …
99
1957 Mo-99m Tc generator (1960 first sale), 133 Xe for lung ventilation
67
1969 Ga accumulation in cancer, C.L.Edwards
1970 Instant KIT’s for 99m Tc
201
1973 Tl and this time 123I, 111In, many other isotopes and tracer compounds
1977 first 18 FDG PET scan

11 million individuals receive every year a radiotracer for diag nosis


Photo published 1942 J.G.Hamilton, M.H.Soley:
“Studies of iodine
metabolism by
thyroid in situ”
1940, Am.J.Physiol. 131, 135

Kidney Isotope Nephrogram


signals
x+, x-, y+, y- GAMMA CAMERA 1958
electronics
Pb shielding
H.O.ANGER
PM tubes

light gide
window
NaI-Detector

collimator

Planar scintigram

Scan Thyroid normal

Pre-amplifier
PM-tube
Pb-shielding
NaI-Detector
Collimator
Object
B.CASSEN
SCANNER
SPECT
Single Photon Emission Computed Tomography

1984 99mTc DMPE


Modern SPET
Cameras
(GE Medical Systems)
NUCLEAR MEDICINE 2000
DIAGNOSIS THERAPIE

SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY) NEW APPROACHES IN


* increase of diagnostic value RADIONUCLIDE THERAPY
* new radiopharmaceuticals * bio-selective antibodies
* dedicated instrumentation & quantification (mab = monoclonal antibodies)
* bio-specific Peptides
PET AS RESEARCH TOOL (Octreotides, others)
* gene therapy
* Molecular in vivo biochemistry
* Gene expression * free chelators like EDTMP
* Clinical research * labelled particles (microspheres, colloids)
* labelled macromolecules
PET AS CLINICAL TOOL NEW RADIONUCLIDES
* Oncology for THERAPY
Reimbursement of FDG-studies * ß- - emitters
* Neurology * α - emitters (213Bi, 149Tb)
* Cardiology

Multi-modality Imaging α-THERAPY & AUGER THERAPY


* combined SPECT-PET PET FOR IN-VIVO DOSIMETRY
(image of the year at the 46.SNM)
* Function and morphology * metallic positron emitters
(PET - CT or SPECT - CT) * labelled drugs
* dose localization
G.BEYER (HUG Geneva, 2000)
ISOTOPES IN MEDICINE
DIAGNOSIS THERAPY
in vitro in vivo internal external

99
14C Mo-99mTc systemic sources tele radio

3H 131I,90Y sealed sources


201Tl 192Ir,182Ta, 137Cs 60Co
125I 153Sm,186Re
123I many others
others 188W-188Re
111In needles for gamma
166Ho,177Lu,
67Ga brachytherapy: knife
81Rb-81mKr
others 103Pd, 125I

α-emitters:
137Cs
many others
others stants blood
225Ac-213Bi cell
32P
ß+ emitters 211At, 223Ra
and others
irradi-
for PET seeds ation
18F, 11C,13N,15O 149Tb 90Sr or 90Y, others
86Y, 124I
68Ge-68Ga e--emitters: applicators
137Cs, others
82Sr-82Rb 125I

G.J.BEYER, HUG Geneva, 2002


141 keV photons - the strength of 99mTc
KIT’s
99mTcO -
4
0.9 % NaCl solution
+

many different
99mTc-tracer
for
imaging of many
different
organ and tissue
functions
HEART
Perfusion

Ventilation study 99mTc


LUNG Function
Perfusion Study
TRACER
Examples

BONE
Metabolic
activity
99 Mo: PRODUCTION ROUTES
98 Mo ( n, γ ) 99 Mo
σ = 0.130 b
1 g 98 Mo, Φn = 1 * 1013 cm-2 s-1
th

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

235 U ( n; f ) 99 Mo

σ = 586 b
99 Mo - fission yield = 6.15 %
1 g 235 U, Φn = 1 * 1013 cm-2
th

914 GBq 99Mo/mg Mo (high specific activity)


ISOTOPE PRODUCTION

Neutron rich
REACTOR ISOTOPES
neutrons

ß- - emitter

High energy proton


induced reactions
EC, α, ß+ - emitter

Proton rich
CYCLOTRON
charged particles ISOTOPES
REACTOR: Problems of RI Production
! Radiation dose targets: elements, oxides, carbonates only, no organic
compounds, material requirements for capsules
! Temperature research reactors usually 60 oC, reactors in power
stations useful for special activations only (60Co)
! Heat production nuclear reaction energy heats up the targets, fission
energy, large target masses – low heat transfer
! Burn out losses of product and generation of impurities,
significant, when σ > 1000 b
! N-depression must be considered when σ > 10 b, lowers yield
! Side reactions impurities with high σ, 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
Problems of medical RI Production with
CYCLOTRONS

• Short range of the particle beam


Range: 30 MeV p about 1 mm
15 MeV d about 0.3 mm
30 MeV a about 0.1 mm

small target - high thermic energy deposition!

• Small cross sections


Low productivity

• Limited and expensive target material


enriched isotopes

• Vacuum
Target window problems, sensitive target material

• Single target – one isotope


Particle Beam Energy
E Ep = 30 MeV,
Ip = 100 µA

p, d, He, Hi
Eth = 3 kW
Area = 1 cm
r
-b 0 +b Range = 1 mm

• at “b” strong nuclear force


• only one particle out of 104……107 reacts in reality
• full particle beam is stopped inside the target material
• the whole particle energy is transformed into thermic
energy (heat)
1 water in
2 water out
3 openings
autoradiogram 4 winding A8

photo autoradiogram

Zn on Cu Backing
14 MeV d, 50 µA
U-120 Cyclotron Rossendorf
1979
BEAM
Target system
for irradiation of
Sensitive target materials
inside the
vacuum chamber of a
cyclotron

Cu3 AS-alloy as
target for the 77 Br
production
FZ Jülich, 1983
Qaim & Stöcklin
IBA Cyclone 18/9, Cyclotron in Geneva
9 MeV Deuteron beam spot
on the Havar Window foil
of the Ne(F2) [18F]F2 target
Ed = 9 MeV, Id = 18 µA, area few mm2

inside the target chamber outside


Excitation function for proton induced reactions

10000

124 124
cross section in mb

Te(p;2n) I
123 123
Te(p;n) I
1000
75
As(p;3n)73Se

100

75
As (p;4n) 72Se
10
0 5 10 15 20 25 30 35 40 45 50
energy in MeV
123-IODINE PRODUCTION ROUTES
5.9 min 2.08 h
123 123 123
Cs EC/ß+ Xe EC I

1985 1980 PSI 1975


Karlsruhe, Canada Würenlingen many places

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


20 – 30 MeV p 75 MeV p 22 – 28 MeV
125 I < 10-3 % 125 I <1% 124 I =1%
ALTERNATIVES:
local 123 I production using PET cyclotrons
123 Te (p,n) 123 I

15 MeV p, 150 MBq/µAh


Fast, easy, reliable, clean product, suitable for direct labeling
irradiated Tl- target
dissolution in 6M HNO3
Fe3+ carrier

hydroxide precipitation
Fe(OH)3 collects 201 Pb Tl
dissolution in 6 M HNO3
Tl
hydroxide precipitation

dissolution in 6M HNO3 Tl

Fe(OH)3 collects 201 Pb

DOWEX 1x8 column Fe


elution with 6 M HCl
Target: 1 – 3 g enriched 203 Tl
decay of 201 Pb,
formation of 201 Tl irradiation with 30 MeV protons
decay period 30 h complete separation of Tl from 201 Pb
reduction of Tl 3+ to Tl1+ 201 decay of 201 Pb into 201 Tl
elution with 3 M HCl Tl 201 Tl
separation of from 201 Pb
Nuclear Medicine Instrumentation
DETECTOR’are
point sensitive place sensitive combined
stationary moving stationary moving
Point collimator multi-hole collimators with / without septa
single detector NaI + many PM’s multi-ring systems
GM / NaI -PM NaI-PM single head 1-3 heads Block detectors BGO

Probe Scanner γ-Camera SPECT PET

67GaCIT 99mTc DMPE


1D 2D 2D 3D 2 D and 3 D
dynamic static dynamic dynamic dyn. & quantitative
ISOTOPES
for Tracer Synthesis
ISOTOPE T 1/2 Reaction Target Product

11C 20 min 14N α) 11C


(p,α N2 unlimited

13N 16O [13N]NH3


10 min (p,α) 13N H2O

15O 2 min 14N (d,n) 15O H2O [15O]H2O

18O (p,n) 18F [18O]H2O [18F]FDG


18F 110 min 20Ne (d, α) 18F 20Ne [18F]FDOPA
IBA CYCLONE 18/9
Cyclotron Unit Geneva
July.2000
Hot Cells

HOT LAB
Cyclotron Unit Geneva
FDG-PET Dementia - Alzheimer’s
PET in oncology
FDG-PET Melanoma therapy control

before

after
Fused Image Tomography
Radiology PET/CT Nuclear Medicine
scanner

Pre Diagnosis
Biopsy
and
Fused image viewer Staging
Post
IMRT
Therapy
response
Surgery Oncology
D.Townsend & T.Beyer, Pittsburg
«Image of the Year » 1999, 46.SNM Los Angeles

D.Townsend, T.Beyer
STATUS PET 2002

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
DIAGNOSIS THERAPIE

SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY) NEW APPROACHES IN


* increase of diagnostic value RADIONUCLIDE THERAPY
* new radiopharmaceuticals * bio-selective antibodies
* dedicated instrumentation & quantification (mab = monoclonal antibodies)
* bio-specific Peptides
PET AS RESEARCH TOOL (Octreotides, others)
* gene therapy
* Molecular in vivo biochemistry
* Gene expression * free chelators like EDTMP
* Clinical research * labelled particles (microspheres, colloids)
* labelled macromolecules
PET AS CLINICAL TOOL NEW RADIONUCLIDES
* Oncology for THERAPY
Reimbursement of FDG-studies * ß- - emitters
* Neurology * α - emitters (213Bi, 149Tb)
* Cardiology

Multi-modality Imaging α-THERAPY & AUGER THERAPY


* combined SPECT-PET PET FOR IN-VIVO DOSIMETRY
(image of the year at the 46.SNM)
* Function and morphology * metallic positron emitters
(PET - CT or SPECT - CT) * labelled drugs
* dose localization
G.BEYER (HUG Geneva, 2000)
ISOTOPES IN MEDICINE
DIAGNOSIS THERAPY
in vitro in vivo internal external

99
14C Mo-99mTc systemic sources tele radio

3H 131I,90Y sealed sources


201Tl 192Ir,182Ta, 137Cs 60Co
125I 153Sm,186Re
123I many others
others 188W-188Re
111In needles for gamma
166Ho,177Lu,
67Ga brachytherapy: knife
81Rb-81mKr
others 103Pd, 125I

α-emitters:
137Cs
many others
others stants blood
225Ac-213Bi cell
32P
ß+ emitters 211At, 223Ra
and others
irradi-
for PET seeds ation
18F, 11C,13N,15O 149Tb 90Sr or 90Y, others
86Y, 124I
68Ge-68Ga e--emitters: applicators
137Cs, others
82Sr-82Rb 125I

G.J.BEYER, HUG Geneva, 2002


CANCER
About 1 000 000 new cancer cases per year in EU
58 % local disease, 42 % generalized
45 % cured (5 year survival)
22 % surgery alone
12 % radiation therapy
6% combination surgery + radiation
5% chemo-therapy
just beginning of systemic radionuclide therapy
HOW: expose cancer cells or cancer tissue
with sufficient radiation doses?
Cancer cases 1997

10000

20000

30000

40000

50000

60000
0
Mund / Rachen

Verdauungsorgane

Cancer Probability in Germany (1997)


Atmungsorgane

Knochen

Bindegewebe

Haut Melanom

Brustdrüse

W. Geschlechtsorgane

Prostata

Hoden

(source RKI)
Penis

Harnblase
F 172 000
M 164 000

Niere

Nervensystem

Schilddrüse

Non-Hodgkin-L.

Hodgkin-Lymphome

Multiples Myelom

Leukämien

Ungenau bez. Lokalisation


ISOTOPES in Therapy =
surgery with radiation
Gamma Auger
Knife ß-Knife α-Knife
Knife
131I, 90Y, 212, 213 Bi, 125I
60Co
ISOTOPE 153Sm,166Ho, 211At, 149Tb, 165Er

others 223, 224Ra

Eγγ > 1 MeV Eß 1 – 3 MeV α 4–8 MeV


Eα Ee few eV
range full body
penetration about 1 cm 30 – 80 µm 1 µm

head RIT
application leukemia future
cancer Radio-immuno therapy

tissue surgery tissue surgery cell surgery molecular


ex vivo in vivo surgery
FDG-PET

Astrocytoma
after treatment
with the
Gamma Knife
Radiation necrosis
in left parietal lobe
RIT = RADIOISOTOPE THERAPY
or RADIOIMMUNO THERAPY
or systemic radionuclide therapy
1936 32 P against leukemia, J.H.Lawrence
1939 89 Sr uptake in bone metastases, C.Pecher
1946 131 I treatment of thyroid cancer, S.M.Seilin et al.
1963 Radioactive colloides, B.Ansell et al.
1976 89 Sr against pain from bone metastases, N.Firusian
1978 Radiolabelled mab, D.Goldenberg
1982 Treatment with 131 I labelled mab, S.Larson et al.
1990 Somatostatine receptor binding tracers, E.Krenning
1993 89 Sr, FDA approval
2000 FDA approval of 131 I-CD20 against Lymphoma ?

Development of therpeuticals is delayed


-
ß
130Te (n,γγ) 131Te 131I

σ = 0.02 b
ß – spectrum 131I
30 h
182 keV IT Eßmax
22 %
25 min
σ = 0.27 b
22 %
78 %
Simplified scheme
8.04 d
for 131I-production via
-
thermal neutron irradiation 131I ß
of natural TeO2
131I Production Technology

Hot Cell Facility


Target Processing
Iodine Trapping
RIT = RADIOI SOTOPE T HERAPY
or R ADIOI MMUNO THERAPY
Nuclide Eßmax Range T½ photons comment
[MeV] [mm] [keV]

90 Y Easy
2.3 4.2 64.1 h no available
Difficult,
188 Re

166 Ho
2.1

1.9 0.7
RIT
17 h

26.8 h
155 keV

(81 keV)
generator

difficult

89 Sr Palliation
1.5 50.5 d no only
186 Re 1.1 90.6 h 137 Carrier

153 Sm 0.8 0.269 46.8 h 103 keV Easy, carrier

131 I most
0.8 8.04 d (364keV) common
177 Lu 0.5 0.147 6.7 d 113/208 Not easy

67 Cu 0.4/0.6 61.9 h 185 Interesting

47 Sc 0.4/0.6 80.4 h 159 interesting

169 Er 0.3 9.4 d no soft


0.1
H.Mäcke, Basle
ALPHA EMITTERS FOR THERAPY

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


229Th (α-decay) 225Ra

224Ra 3.66 d 233U decay chain


228Th (α-decay) 224Ra

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


227Th (α-decay) 223Ra

213Bi 45.6 m 225Ac decay chain Ac–Bi generator


212Bi 60 m 224Ra decay chain Ra–Bi/Pb generator
211At 7.2 h 209Bi (α,2n) 211At
149Tb 4.1 h Ta (p,spall)
152Gd (p,4n) 149Tb
Principle of Radioimmunio Therapy

Cell membrane
DAUDI cells 149Tb

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

MoAb (Rituximab)
specific to
CD20 antigens
of B cells
Protein strand in cancer cells
(CD20 antigens of B cells)
Plasma
134Ce/La 140Nd/Pr 149Tb

Positron emitting radio-lanthanides for individual in vivo dosimetry


PET phantom studies
142SmEDTMP in vivo study

138Nd/Pr 142Sm/Pm 152Tb


The Geneva PET and CERN
CERN: the world largest
acceleartor complex for fundamental
particle physics research
ISOLDE: the world leading on line
isotope separation facility and provides
- universal access practically to all
radionuclides
- in unprecendented purity,
very useful for biomedical research,
integrated into the
Geneva PET Program
(in vivo dosimetry based on PET)
142-SmEDTMP, 60 min p.i.
3D whole-body PET
ECAT HR+ ECAT ACCEL
25 year-old male with Melanoma, 50 year-old male with colon CA
71 kg, 178 cm, 625 MBq FDG, 45 min p.i. 91 kg, 183 cm, 720 MBq FDG, 162 min p.i.

Emission scan time: 54 min


Emission scan time: 27 min
Transmission scan time: 18 min
Transmission scan time: 18 min
Data courtesy of Data courtesy of
Kettering Memorial Hospital, Kettering, USA NC PET Imaging Center, Sacramento, USA
RADIOISOTOPES in MEDICINE:
Trends – Market – R&D (1)

US only
Resume from the
Medical Isotope Workshop, Dalles, (Texas) May 2-3, 1998

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 6’000 * 106 US-$
RADIOISOTOPES in MEDICINE:
Trends – Market – R&D (2)

Market : Brachytherapy (Prostate) 1998 100 * 106 US-$


Bill EHMIG increasing 125I, 103Pd seeds
…… huge market (14 cyclotrons only for 103Pd)
trend: …… change from palliation to cure !
Other sources: lymphome therapy “Curie Therapy”
131I-LYM-1 mab, US only 100 * 106 US-$ /y
(today 131I -CD-20-mab up to 0.8 Ci dose/patient)
HOW ?
Henry WAGNER: … full radiotracer development program,
not just radionuclide development…
… a national governmental facility provides the
infrastructure, industry provides the distribution
network…
TRENDS - OUTLOOK

80 % of worldwide produced radioisotopes


are 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.

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