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MEDICINE:
Requirements – Production - Application
Gerd-Jürgen BEYER
Prof.Dr.habil.
Cyclotron Unit,
University Hospital of Geneva,
Division of Nuclear Medicine
Switzerland
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
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)
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.
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
99
14C Mo-99mTc systemic sources tele radio
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
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
light gide
window
NaI-Detector
collimator
Planar scintigram
Pre-amplifier
PM-tube
Pb-shielding
NaI-Detector
Collimator
Object
B.CASSEN
SCANNER
SPECT
Single Photon Emission Computed Tomography
99
14C Mo-99mTc systemic sources tele radio
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
many different
99mTc-tracer
for
imaging of many
different
organ and tissue
functions
HEART
Perfusion
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
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
Neutron rich
REACTOR ISOTOPES
neutrons
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
• Vacuum
Target window problems, sensitive target material
p, d, He, Hi
Eth = 3 kW
Area = 1 cm
r
-b 0 +b Range = 1 mm
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
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
hydroxide precipitation
Fe(OH)3 collects 201 Pb Tl
dissolution in 6 M HNO3
Tl
hydroxide precipitation
dissolution in 6M HNO3 Tl
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
99
14C Mo-99mTc systemic sources tele radio
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
10000
20000
30000
40000
50000
60000
0
Mund / Rachen
Verdauungsorgane
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
head RIT
application leukemia future
cancer Radio-immuno therapy
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 ?
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
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
131 I most
0.8 8.04 d (364keV) common
177 Lu 0.5 0.147 6.7 d 113/208 Not easy
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
US only
Resume from the
Medical Isotope Workshop, Dalles, (Texas) May 2-3, 1998