99mTc
Production of Medical
isotope
via Photoreaction and neutron
absorption
EMIN2015
Moscow State University, 7 October 2015
M. Fujiwara (RCNP, Osaka Univ. & JAEA)
Collaborators: K. Nakai, N. Takahashi (Osaka Univ.)
T. Hayakawa, T. Shizuma (JAEA),
S. Miyamoto, G. Fan, A. Takemoto,
M. yamaguchi (Hyogo Univ.),
M. Nishimura (Kyocera)
99Mo
(T1/2=66 h) production from 235U using research nuclear reactors
Patten, Netherlands
Supply ends 2022
Chalk River, Canada
Supply ends 2016
99Mo
supply in the world
Country operation rate supply
(%)
(%)
Canada
86
38
Netherlands 79
26
Belgium
31
13
France
60
3
South
Africa
86
15
All the research reactors were constructed around 1960 after “Atoms for Peace” of Eisenhower,
and they are now older than 40 years. The used HEU (Highly Enriched 235U fuel) tends to be
prohibited due to PTBT (Partial Test Ban Treaty, 1963) and NPT (Treaty on the Non-Proliferation
of Nuclear Weapons, 1968).
Annual radiation dose of Japanese: 3.8 mSv
Earth gamma
radiation
0.46 mSv (12%)
Cosmic
0.29 mSv (8%)
Food, water
0.4 mSv (10%)
Radon (natural
internal exposure)
0.4 mSv (10%)
Human made
source
0.04 mSv (1%)
Medical
2.25 mSv (59%)
99mTc
99Mo/99mTc
milking
1. The half-life of 99Mo is 66 hour.
2. The half-live of 99mTc is 6 hour.
Long distance transportation is
impossible.
3. 99Mo decay is used for 99mTc milking,
and is used for SPECT medical
imaging.
K. Nakai et al., Proc. Jpn. Acad., Ser B 90 (2014) 413.
Report from Bio-Tech Systems, Inc. USA (2007)
99Mo/99mTc
4%
consumption
other
44%
12%
22%
USA
Europe
Japan
Canada
other
In Japan, 99mTc is used in hospitals for SPECT imaging of about
1,000,000 patients. 2000 TBq 99mTc in total is imported from abroad
with the cost of 100 US million dollar.
1.
99Mo
isotopes are mainly produced by neutron induced fission
from highly enriched 235U in research reactors.
2. Market size for 99mTc SPECT:
Japan: 1,000 M$ (99Mo cost 100 M$) about 1,000,000 patients
US:
3,000 M$ (99Mo cost 300 M$)
All of 99Mo medical isotopes are imported from foreign countries.
3. HEU will not be used any more because of NTP and Nuclear
Terrorism. US distributed 21 tons of HEU and Russia distributed
11 tons of HEU for research nuclear reactors.
4.
In case of use LEU,
239Pu
is produced. How can we treated it?
In April-June 2010, 99Mo supply shortage happened due to that the
Iceland volcanic eruption ash stopped all the flights from
Europe and due to the trouble of Chalk River nuclear reactor.
Important Items for Nuclear Security (After 1970)
1974/5: Atomic bomb test in India
1972/3: IAEA Safeguard
1979: Atomic bomb test in South Africa
1978: NSG guidelines Part I
1991/12: Dissolution of the
Soviet Union
Flow-out of nuclear materials,
atomic bomb technologies ?
1998/5: Atomic bomb test in Pakistan
1987/2: treaty of protection of nuclear material
2001/9.11 terrorism in US
US was forced to take prompt nuclear
terrorism measure .
1992: NSG guidelines Part II
1995: IEAE data base for illegal trade of nuclear
materials
2004/4: United Nations security Council Resolution 1540
for nonproliferation of Weapons of Mass Destruction
(WMD)
2005/7: revision of treaty of protection of nuclear
material: Safeguard Strengthen of nuclear power
plants in Japan
2006/7: Global Initiative to Combat Nuclear
Terrorism（GICNT） in G8 summit: Prevention,
detection and response to a nuclear terrorism event
2010/4: 1st Nuclear security summit
2012/3: 2nd Nuclear Security summit
2014/3: 3rd Nuclear Security summit
2003/12: Libiya declared the abolition of weapon
of mass destruction (WMD)
It was found that Abudul Khan operated the black
market of nuclear materials and technologies.
2006/10: Atomic Bomb test in North Korea
2007/11: Slovak police
found enriched 0.5kg
Uranium
2007/7: treaty to deal with nuclear terrorism
Integrated Support Center for Nuclear Nonproliferation and
Nuclear Security (ISCN ) for in Japan
Reinforce of safeguards on nuclear facility in Japan
？
Increase of nuclear
terrorism
Incidents involving HEU and Pu in 1993-2007 (IAEA report)
1993-05 Vilnius Lithuania
1994-03 St.Petersburg Russia
1994-05 Tengen-Wiechs, Germany
1994-06 Landshut, Germany
1994-07 Munich, Germany
1994-08 Munich Airport, Germany
1994-12 Prague, Czech
1995-06 Moscow, Russia
1995-06 Prague, Czech
1995-06 Ceske, Czech
1999-05 Rousse, Bulgaria
2000-12 Karlsruhe, Germany
2001-07 Paris, France
2003-06 Sadahlo, Georgia
2005-03 New Jersey, USA
2005-06 Fukui, Japan
2006-02 Tbilisi, Georgia
2006-03 Hennigsdorf, Germany
2007-11 Slovakia
HEU/ 150 g
HEU/ 2.972 kg
Pu/ 6.2 g
HEU/ 0.795 g
Pu/ 0.24 g
Pu/ 363.4 g
HEU/ 2.73 kg
HEU/ 1.7 kg
HEU/ 0.415 g
HEU/ 16.9 g
HEU/ 10 g
Pu/ 0.001 g
HEU/ 0.5 g
HEU/ ~170 g
HEU/ 3.3 g
HEU/ 0.0017 g
HEU/ 79.5 g
HEU/ 47.5 g
HEU/0.5 kg
discovered in the storage area of a bank.
a trader illegally kept stolen HEU for sale.
plutonium was detected in a building.
a group of individuals with illegal HEU.
confiscated a small sample of PuO2-UO2.
PuO2-UO2 mixture at Munich airport.
a trader illegally kept HEU for illegal sale.
a trader illegally kept HEU for illegal sale.
An HEU sample was seized by police.
An HEU sample was seized by police.
Customs officials arrested a smuggled HEU.
stolen from the pilot reprocessing plant.
buyers were arrested with HEU material.
an smuggler was arrested across the border.
3.3 g HEU was disposed.
a neutron flux detector was lost at an NPP.
traders were arrested trying to sell HEU.
found in amidst scrap metal.
police found enriched 0.5kg uranium
99Mo
production
Photoreaction cross sections on 100Mo
Sp=11.146 MeV
96Mo(g,n)95mNb
(86.6 h)
EPJ Web of Conferences 66, 03077 (2014)
Proposed plan at J-PARC
K. Nakai et al., Proc. Jpn. Acad. Ser. B 90 (2014) 413
Photo of J-PARC
(n,2n) from neutron
Source by a 400 MeV
proton beam
PET cyclotron for 99mTc production
K. Nakai et al., Proc. Jpn. Acad. Ser. B 90 (2014) 413
99mTc
generator
Mo-Tc separation device (Tc generator) by N. Takahashi (Patent 2012224859 (domestic) and Patent 2014/057900A1 (international)) .
• US Nuclear Science Advisory Committee report on 30 July 2015:
99Mo shortage happen during 2016-2018.
• US tends to use LEU for 99Mo production.
• Canada seeks the feasibility of 𝑝, 𝑝𝑛 and (𝛾, 𝑛) reactions.
• In Japan, the discussion started in 2012 after the 99Mo shortage
in 2010. The possibility to use the 𝑝, 𝑝𝑛 , 𝑛, 2𝑛 , 𝛾, 𝑛 , (𝑛, 𝑓)
reactions are searched for. However, still we do not obtain the final
conclusive answers.
Osaka Univ. now seeks the feasibility of 𝑝, 𝑝𝑛 and (𝛾, 𝑛) reactions.
JAEA (Nagai et al., ) group is looking for (n,2n) reaction.
Always, a serious problem is expensive price of enriched 100Mo.
QTY (g)
Enrichment
US$/gram
total
50
80%
1,100
55,000 $
100
80%
980
98,000 $
500
80%
800
400,000 $
1000
80%
575
575,000 $
How can we resolve the high cost problem of
medical imaging?
Answer is the test to use natural materials.
1. Natural Mo: 100Mo 𝛾, 𝑛 99Mo or 98Mo 𝑛, 𝛾
1. Depleted Uranium: 238U(g,f).
2. Thorium: 232Th(g,f).
99mTc
99
Mo
nuclear waste (fission
products with long half-lives)
Sustained Availability of 99mTc:
Thermo-separation of 99mTc from 99Mo by Sublimation
1. R.H. Busey and Q. V. Larson, ORNL-2584 (1958) pp.5.
2. E. Anders, Annu. Rev. Nucl. Sci. 9 (1959) 203.
2. In book by Klaus Schwochau, Technetium: Chemistry and
Radiopharmaceutical Applications, WILEY,
ISBN:978-3-527-61337-3 (2008).
2. I.D. Christian et al., Advances in sublimation separation of
technetium from low-specific-activity modibdenum-99.
Ind. Eng. Chem. Res. 39 (2000) 3157.
3. J. Gerse, J. Kem, J. Imre, L. Zsinka, Examination of Portable
99Mo/99mTc isotope generator: SUBLITECH. J. Radioanal Nucl.
Chem. 28 (1988) 71.
4. R.G. Bennett et al., US Patent 5802439 (1998).
5. A.V. Sabel’nikov et al., Radiochemistry 48 （2006) 191.
Mainly from (n, g) reaction
After Fukushima Dai-ichi nuclear power plant accident in 2011,
Japanese nuclear reactors has stopped for long time.
Possible Sustainable Path in Japan toward self-supply of 99mTc.
Use electron accelerators for (g,n) reaction to produce 99Mo isotopes
Solve the Engineering Problems
50 MeV electron bombardment from Bremsstrahlung g-rays:
3000 Bq/mg/mA/h @ 50 MeV (Kikunaga, Tohoku Univ.)
3ｘ103x104x104x101x10-1 Bq/10 g/10 mA/10 h at 50 MeV
0.3 TBq/10 g of natural MoO3
In Japan, 2000 TBq of 99Mo is imported every year for 106 patients.
About 2 GBq of 99Mo is used for one SPECT inspection.
However, about 200 MBq of 99mTc is used for one SPECT inspection
due to the extraction efficiency of 99mTc from 99Mo, and decay of 99Mo
and 99mTc.
Melted MoO3 powder
Transparent crystalline solid
from MoO3 powder on the inner
wall of the quartz glass
Deeply sintered
MoO3 at temperature of
below 795 ℃
sintered MoO3 at moderate high
temperature around 740℃
Almost all MoO3 powders are melted at around T=795°C,
and the volume becomes small.
MoO3 powder
MoO3 powder after heating up at 600℃
M=2000
10 mm
M=200
100 mm
M=2000
10 mm
M=200
100 mm
MoO3 target with a thickness of 9 g/cm2
LCS g-ray facility
Utsunomiya et al., IEEE Transaction
on Nuclear Science 61 (2014) 1252
MoO3 powder
capsule
SiC 1000 ceramic
Al2O3
Alumina ceramic
Ceramic
(Kyocera product
name)
Thermal
Conductivity
(W/m・K at 20℃)
Materials
(Metal)
Thermal
Conductivity
(W/m・K at 20℃)
SiC (SC1000)
200
Silver (Ag)
407
AN (AN216A)
150
Cupper (Cu)
381
Al2O3 (SA100)
41
Gold (Au)
299
Si2N4 (SN240)
27
Iron (Fe)
56
Sublimation of 99mTc (dry method)
gas
We put tungsten powder
in the SiC tube
Wet chemical method by N. Takahashi
Summary for 99Mo production in Japan
(1) 2000 TBq requirement of
99Mo
in Japan every year: all from
foreign countries. 100 M$ is used for 99Mo every year, and
1000 M$ medical cost for patients. US also imports 99Mo by
paying 300 M$ every year.
(2) Mo shortage will come in 2016-2018 due to the 99Mo supply
stop of Canada.
(3) We need to move toward the self-support of 99Mo by taking
into account all scientific, political and commercial situations.
(4) We discuss the feasibility of sustainable use of natural Mo
powder in extracting 99mTc from the natMo(g,n) reaction.
(5) 0.3 TBq/day*300 day*20 =1800 TBq  20 small electron
LINAC accelerators are enough to satisfy all the 99Mo
requirements in Japan.
(6) Both the dry (sublimation) and wet (chemistry) methods will
work to extract 99mTc isotopes.