technetium: mo/ tc “generators” and production of tc...
TRANSCRIPT
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Technetium: 99Mo/99mTc “generators”and production of Tc radiotracers
*Board of Interdivisional Group of Radiochemistry, GIR
Italian Society of Chemistry, SCI
*Mauro L. Bonardi and Flavia GroppiRadiochemistry Laboratory, LASA
Universita’ degli Studi and INFN, Milano, Italy
Collaborations: JRC-Ispra-EC, IAEA-NDS, ATOMKI-Debrecen-HU,Beer Sheva-Israel, INR-Russia, NIST-USA, LANL-USA,
TRIUMF-CA, ORNL-USA, iThemba LABS-SA
http://wwwGIR.mi.infn.it
*EuCheMS-Division NRC, ANS-IC
[email protected] [email protected]
International Union of Pureand Applied Chemistry
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Main steps in accelerator (or reactor) production of a labelled compound (e.g. radiopharmaceutical)
The Quality Control (QC) and God Manufacturing Practice (GMP) are mandatory for each step of the procedure
In a selected number of cases, it is possible to avoid the radiochemical ich happens in target itself: recoil labelling with hot atomsprocessing step, wh
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99Mo
87.6
%
36Kr 37Rb 38Sr 39Y 40Zr 41Nb 42Mo 43Tc 44RuISOBAR-99
99mTc
35 36 37 38 39 40 41 42 43 44 45
10-1210-1110-1010-910-810-710-610-510-410-310-210-1100101
RbNb
YSrZr
Kr
inde
pend
ent f
issi
on y
ield
(%)
atomic number , Z
Tc
Mo
Independent Fission Yields (%) of thermal neutrons on U-235
isobar-99 comulative yield = 6.161% gaussian model
β − decay
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Z.B. ALFASSI, M.L. BONARDI, J.J.M. De GOEIJ, F. GROPPI, On the “carrier-free” nature of 99mTc, Appl. Radiat. Isot., 63 (1) (2005) 37-40.
Simplified decay scheme of isobar-99 and Mo-Tc “generator”The 99mTc is never a carrier-free radionuclide due to the unavoidable presence of the long-lived 99gTc isotopic carrier
W.C. ECKELMAN, M. BONARDI, W.A. VOLKERT, True radiotracers: are we approaching theoretical specific activity with Tc-99m and I-123?, Nucl. Med. Biol., 35 (5) (2008) 523-527.
Present WorldDemand
450.000 GBq/week12.000 GCi/week
[email protected]@mi.infn.it
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• Classical Nuclear Reactor Methods for production of 99Mo 99mTc “generator”
*(HEU 99 %) U-235 (n,fiss) Mo-99 thermal neutrons 36.10 barn # (σfiss = 586 b)(liquid LEU 20 %) U-235 (n,fiss) Mo-99 thermal neutrons 7.22 barn #
#normalized to 6.161 barn of isobar 99 on 235U
*Mo-98 (nat 9.63 %) (n,γ) Mo-99 thermal neutrons 0.14 barn
• New Possibilities via 99Mo 99mTc “generator”*Mo-100 (nat 9.63 %) (n,2n) Mo-99 neutrons 6 - 17 MeV 1.5 barn $
$ Yasuki NAGAI, Yuichi HATSUKAWA, Production of 99Mo for Nuclear Medicine by 100Mo(n,2n)99Mo, J. Phys. Soc. Japan Letter, 78 (3) (2009)
033201*Mo-100 (γ,n) Mo-99 $GDR 10–30 MeV photons (bremstrahlung, Thomson)*Mo-100 (p,pn) Mo-99 15 – 64 MeV protons 158 mbarn (max)*Mo-98 (n,γ) Mo-99 %ARC thermal-epi neutrons from protons 1 GeV, 1 mA*[Mo-98]complex Szilard-Chalmers Mo-99 thermal-epithermal neutrons > 0.14 barnU-nat (p,fiss) Mo-99 70 MeV protons about 30-50 mbarnU-nat (d,fiss) Mo-99 fast deuterons U-nat (γ,fiss) Mo-99 10 – 30 MeV fast photons (bremstrahlung, Thomson)
*Zr-96 (nat 6.8 %) (α,n) Mo-99 15 – 35 MeV alphas
• Direct production of 99mTc from molybdenum target ( without “generator )*Mo-100 (nat 9.63 %) (p,2n) Tc-99m (+Tc-99g) 12 – 22 MeV 200 mbarn (max)*Mo-98 (p,γ) Tc-99m (+Tc-99g) 30 – 50 MeV 130 mbarn (max)
*Mo-98 (d,n) Tc-99m (+Tc-99g) 10 – 35 MeV
* high enriched target $ Giant Dipole Resonance % Adiabatic Resonance Crossing
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Cross-sections of neutrons on 98Mo
1 / v law
several resonances
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Radiative neutron capture cross section of 98Mo(n,γ)99Mo , (the epithermal contribution could be substantial)
epithermal
thermal neutrons
0.14 barn
0.02
5 eV
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fiss CB for protonson 238U = 12.3 MeV
10 MeV p
100 MeV p
Fission of 238U with 70 MeV protonsthe σ of isobar—99 is about 30-50 mbarn
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In radiochemistry, the short half-life must gain a radiochemical yield (RCY) larger than the chemical yield (CY) of conventional chemistry. The blue line represent in
semilog scale the decay of radionuclide during the radiochemical steps.EOP: End Of radiochemical Processing
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The “generators” : 99Mo 99mTc
The classical and widespread 99Mo 99mTc generator is based on a small radiochromatographic column (normally of stainless steel) filled with a few cm3 of acidic alumina (AAO or acidic Al2O3) and the single charged aqua-anion TcO4- is eluted with a physiological saline solution (NaCl 0.9 %), while the double charged anion MoO42- is strongly retained onto the column (see next slides).
Other generators based on different filling materials:• gel of zyrconium molybdate, for large volume samples starting from either liquid LEU
or highly enriched 98Mo targets
• performances of nanoparticellar zyrconia vs. alumina
• PZC: solid support of nanocomposites of polyzirconyl anion exchanger
• PTCs: different kinds of Phase Transfer Catalysts (enhance velocity of either nucleofilic substitution or electrofilic addition/substitution smaller reagent and solvent volumes), for low-medium activity
• DOWEX-1x8 or AG1x8 strong anion exchanger, for low-medium activity (radiation damage due to the organic lattice)
Electrochemical generator (similar to 90Sr/90Y one, developed in India)
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13
Present World
Demand450 TBq/week12 TCi/week
2sterilysing
filter
TcO
4-el
uted
Mo
2-ad
sorb
ed30
cm
4
15 cm
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TcO
4-el
uted
100
% ?
Mo 4
2-ad
sorb
ed10
0 %
?
15 cm
30 c
m
15 cmPresent World
Demand
450 TBq/week12 TCi/week
2
3
sterilysingfiltern
o M
o
brea
kthr
ough
!
X
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Elution profile of 99mTc from a 99Mo “generator”(the elution is carried out as a rule every 24 h)
99Mo
99mTc
87.6
%
Tmax = 22.83 h withdecay branching
of 100 %
0 24 48 72 96 120
10
100
time (days)
99M
o an
d 99
mTc
act
ivity
(%)
time (hours)
0 1 2 3 4 5
elut
ion
6
elut
ion
5elut
ion
3
elut
ion
2
elut
ion
1
RCY of elutions 100 %
elut
ion
4
decay branching100 % (black dots)
realbranching87.6 %
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Taken from Dewi M. Lewis (GE) and Natesan Ramamoorthy, IAEA, Vienna , WORKSHOP “PHYSICS FOR HEALTH IN EUROPE”, CERN 02 - 04 Feb 2010
1 Accelerator or Research Reactor
facility for target irradiation
The accelerators are normally cyclotrons or linac (light ions and electrons for intense
photon beams)
2 Radiochemical Processing in a
series of Hot-Cells and master-slave
manipulators
3 Partitioning of bulk activity after QC under GMP
rules and restrictions
Schematics of main stepsin commercial production
of radionuclides and radiopharmaceuticals
[email protected]@mi.infn.it
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Hot Cell facility for radionuclide processing at LANLEach cell dedicated to 1 different radionuclide or radiopharmaceutical
Master-Slave manipulators
Pb glass windows
Manip Hand Hood
Dis
pens
ary
Cel
lWarm Corridorfor maintenance
Cell1
Cell2
Cell3
Cell4
Cell5
Cell6
Cell7
Cell8
Cell9
Cell10
Cell11
Cell12
Cell13
Foye
r
TrainMaintRoom
Dis
solv
ing
Ben
ch
train
railw
ay
Master Cell
Train for activity
distribution
M-S
man
ipul
ator
s
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Mauro Bonardi, Claudio Birattari, FlaviaGroppi, Enrico Sabbioni, Thin-target excitation functions, cross-sections and optimised thick-target yields for natMo(p,xn)94g,95m,95g,96(m+g)Tc nuclear reactions induced by protons from threshold up to 44 MeV. No Carrier Added radiochemical separation and quality control, Appl. Radiat. Isot., 57 (5) (2002) 617-635.
Other radionuclides of technetiumproduced in a proton cyclotron via
Mo(p,xn) reactions for research purposes (Milano and Ispra 1982 – 2004)
• Claudio Birattari, Mauro Bonardi, Marco Castiglioni, J. Edel, Monica Gattinoni, F. Mousty, Enrico Sabbioni, Gamma-emitting technetium radiotracers production for waste disposal studies at Milan AVF Cyclotron,Report INFN, INFN/TC-84/24, Frascati, Roma, 1984
• Andrea Marchi, Licia Uccelli, Luciano Magon, Mauro Bonardi, Mario Gallorini, Flavia Groppi, Sabrina Saponaro,
Technetium complexes with ligands of pharmacological interest, J. Radioanal. Nucl. Chem., 195 (1995) 237-242.• Mauro Bonardi e Flavia Groppi, Masurio-99m, Masurio-99, Renio-186g, Renio-188,: Radioelementi chimici isomorfi, ma
con attività specifica e proprietà chimico-fisiche differenti. Storia e produzione di radiotraccianti. Metodiche di produzione e controllo di qualità, Rapporto INFN/TC-01/04, Frascati, Roma, 2001
0 5 10 15 20 25 30 35 40 450
2
4
6
8
10
12
14
16
18
20
22
24 94gTc 95gTc
95mTc*103
96(g+m)Tc
Thin
Tar
get Y
ield
(GB
q/C
MeV
)
Proton Energy (MeV)
[email protected]@mi.infn.it
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Ciclotrone 70 MeV
[email protected] and [email protected]
IUPAC
Technetium: 99Mo/99mTc “generators” and production of Tc radiotracersSimplified decay scheme of isobar-99 and Mo-Tc “generator”The 99mTc is never a carrier-free radionuclide due to the unavoidaRadiative neutron capture cross section of 98Mo(n,g)99Mo, (the epithermal contribution could be substantial)Fission of 238U with 70 MeV protons the s of isobar—99 is about 30-50 mbarnThe “generators” : 99Mo 99mTcElution profile of 99mTc from a 99Mo “generator”(the elution is carried out as a rule every 24 h)Hot Cell facility for radionuclide processing at LANLMauro Bonardi, Claudio Birattari, Flavia Groppi, Enrico Sabbioni, Thin-target excitation functions, cross-sections and optimi