Feasibility studies towards future self-sufficient supplyof the 99Mo-99mTc isotopes with Japanese accelerators

By Kozi NAKAI,*1,† Naruto TAKAHASHI,*2 Jun HATAZAWA,*3 Atsushi SHINOHARA,*2

Yoshihiko HAYASHI,*2 Hayato IKEDA,*3 Yasukazu KANAI,*3 Tadashi WATABE,*3

Mitsuhiro FUKUDA*1 and Kichiji HATANAKA*1

(Communicated by Toshimitsu YAMAZAKI, M.J.A.)

Abstract: In order to establish a self-sufficient supply of 99mTc, we studied feasibilities toproduce its parent nucleus, 99Mo, using Japanese accelerators. The daughter nucleus, 99mTc, isindispensable for medical diagnosis. 99Mo has so far been imported from abroad, which is separatedfrom fission products generated in nuclear reactors using enriched 235U fuel. We investigated 99mTcproduction possibilities based on the following three scenarios: (1) 99Mo production by the (n, 2n)reaction by spallation neutrons at the J-PARC injector, LINAC; (2) 99Mo production by the (p, pn)reaction at Ep F 50–80MeV proton at the RCNP cyclotron; (3) 99mTc direct production with a20MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for ascheme on a global scale, scenario (2) works in a local area, and both cases take a long time fornegotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for99mTc production. We here consider both the advantages and disadvantages among the threescenarios by taking account of the Japanese accelerator situation.

Keywords: 99Mo-99mTc, Accelerator production, J-PARC, PET-cyclotron, Tc generator

1. Introduction

The radioisotope 99mTc has long been usedfor medical diagnostic imaging with the SPECT(Single Photon Emission Computed Tomography) inmany hospitals and medical facilities (as many as1,200). Throughout the long history of radio-medicalapplications, various chemicals labeled by 99mTcradioactive isotopes have been developed for medicalexamination1) (e.g. blood flow, bone metastasis, etc.;see Table 1).

The isotope supply in Japan is mostly fromabroad, which may possibly have catastrophicimpacts on medical activities when some difficulties

might occur concerning the import of 99Mo isotopesfrom abroad in the future. In this paper, we discussthe feasibility for the self-sufficient supply of the99mTc isotope in Japan.

The short half-life of 99mTc (T1/2 F 6.02 hr)makes a convenient delivering system impossible.However, the 99mTc isotope is generated throughthe radioactive decay of 99Mo (T1/2 F 66.0 hr), whichcan be easily transported over long distances tohospitals.

The 99Mo isotope has been mostly generated innuclear reactors using highly enriched 235U fuel(HEU). However, presently, the use of HEU tendsto be prohibited due to PTBT (Partial Test BanTreaty, 1963) and NPT (Treaty on the Non-Proliferation of Nuclear Weapons, 1968), so thatthe only 5 HEU reactors are in operation world-wide.All of them are more than 50 years old, and are nowsuffering from various problems. Therefore, we arenow encountering a serious problem: that the supplyof 99Mo isotopes may often become unstable, andthat any 99Mo isotope shortage will reach a crisislevel in medical diagonosis.2)

*1 Research Center for Nuclear Physics, Osaka University,Osaka, Japan.

*2 Graduate School of Science, Osaka University, Osaka,Japan.

*3 Graduate School of Medicine, Osaka University, Osaka,Japan.

† Correspondence should be addressed: K. Nakai, ResearchCenter for Nuclear Physics, Osaka University, 10-1 Mihogaoka,Ibaraki, Osaka 567-0074, Japan (e-mail: nakai@post.kek.jp).

Proc. Jpn. Acad., Ser. B 90 (2014)No. 10] 413

doi: 10.2183/pjab.90.413©2014 The Japan Academy

Since the present 99Mo production scheme usingHEU violates the regulations of PTBT and NPT,we need to develop alternative methods.3) Togetherwith world-wide efforts, new methods to produce the99Mo isotopes have been explored and proposed usingJapanese accelerator facilities through photonuclearreactions (., n),4) neutron-induced reactions (n, 2n)5)

and (n, .), as well as proton-incident reactions (p, pn)and (p, 2n).

We started feasibility tests in generating neu-trons6) from the high-energy, high-intensity protonbeam of the injector LINAC (Linear Accelerator)of J-PARC (Japan-Proton Accelerator ResearchComplex). In this paper, we report on a series offeasibility-test experiments at the Ring-Cyclotronfacility of RCNP (Research Center of NuclearPhysics). While the J-PARC/injector LINAC couldprovide a 400MeV, 300 µA beam, a proton beam of400MeV, 1 µA is available at the RCNP/Ring-Cyclotron. The latter has been a nice playground totest the basic ideas and various feasibilities becauseof easier access and convenience for experimentaldesigns. We also studied the possibilities of usinglower energy proton beams for 99Mo production aswell as 99mTc direct production by using the AVF(Azimuthally Varying Field) cyclotron.

2. Production of 99Mo isotopeswith spallation neutrons

In nuclear reactions using projectiles above100MeV/nucleon, the collision speed becomes fasterthan the nucleon Fermi motion in nuclei, or above

the sound velocity of nuclear matter. Therefore, theneutron yield increases dramatically through thespallation process (see Fig. 1). We expect to increasethe 99Mo yield via the 100Mo(n, 2n)99Mo reaction. Forproducing medical isotopes, however, the specificactivity is an additional factor to optimize the protonenergy. We used a 400MeV proton beam on aheavy-metal target to produce spallation neutrons,so that the 99Mo isotope would be produced viathe 100Mo(n, 2n) reaction on a natural Mo target.A heavy-metal Mo, Ta, or W target was used togenerate fast neutrons by the (n, xn) reaction. Weused the Monte-Carlo program ‘PHITS’7) (Particleand Heavy Ion Transport code System) for designingthe experiments. An example of the PHITS simu-lation for neutron emission from 400MeV protons ona thick Ta target is shown in Fig. 2. In contrast tothe forward-enhanced distribution at low incidentenergies, lower than 100MeV, spallation neutronsare emitted sideways. Hence, a cylindrical targetconfiguration is favorable when using neutrons forthe 100Mo(n, 2n) reaction. Figure 3 shows a typicalspectrum of spallation neutrons. In this figure, theproduction cross section for the 100Mo(n, 2n)99Moreaction is inserted. The neutron yields decreasemonotonically with increasing the neutron energy.Thus, the overlaps between the neutron yields andthe 100Mo(n, 2n)99Mo cross section is not ideally good.However, there was almost no way to change theneutron spectrum shape. The high-energy protonbeam allows us to use a thick target, as long as15 cm.

Table 1. 99mTc Radioactive medicines (from Ref. 1)

Brain 99mTc-DTPA, 99mTcO4, 99mTc-HMPAO, 99mTc-ECD

Thyroid gland 99mTcO4!

Lungs 99mTc-MAA*, 99mTc-colloid, 99mTc-HAS (* added by present authors)

Heart 99mTc-sestamibi, 99mTc-tetrofosmin, 99mTc-pyrophostate, 99mTc-red blood cell

Vein 99mTc-MAA

Liver 99mTc-phytate, 99mTc-Sn colloid, 99mTc-HIDA, 99mTc-PMT

Salivary gland 99mTcO4!

Meckel diverticle 99mTcO4!

Gastrointestinal tract 99mTc-red blood cell

Kidney 99mTc-DMSA, 99mTc-MAG3, 99mTc-DTPA

Testicles 99mTc-HSA

Placenta 99mTc-HSA

Spleen 99mTc-Sn colloid

Bone 99mTc-MDP, 99mTc-HMDP

Lymph node 99mTc-Re colloid, 99mTc-Sn colloid

K. NAKAI et al. [Vol. 90,414

3. Feasibility studies at RCNP for proposingthe project at J-PARC

In order to propose a 99Mo-99mTc productionproject at J-PARC, we carried out a series ofexperiments using the 400MeV proton beam at theRing cyclotron of RCNP. With the target config-uration set to use the cylindrically distributedspallation neutrons, as shown in Fig. 2, experimentswere carried out to test 99Mo production. A 400MeV35nA proton beam was incident on a neutron-production target of a natural Mo rod with 15mmdiameter and 150mm length. The range of 400MeVprotons in a metallic Mo target was calculated to be128mm. Neutrons were emitted sideways along thebeam axis in the Mo target. For determining the99Mo production rate, we used natural Mo pellets of10mm diameter and 1mm thickness set along theside of the neutron production target. The irradiation

time was 0.5 hr with a beam intensity of 35 nA, i.e.1/10,000 of the J-PARC beam. The next day, aftercooling any background activities, .-ray analyseswere performed to determine the yield. The resultshowed that the 99Mo yield obtained by bombardingthe 400MeV 35 nA proton beam for 0.5 hr on anatural Mo target was at least 10 kBq/g. As shown inFig. 4, the 99Mo yield expected in the case of J-PARCusing the 400MeV 330 µA proton beam for 10 hr isgiven by

ð10 kBq=gÞ � ð330 �A=35 nAÞð10 hr=0:5 hrÞ� 2GBq=g=10 hr

If a 500 g natural Mo target is used, we expect toobtain 1TBq/10 hr. We propose to add this functionto the J-PARC/injector-LINAC as a parasite job tobe operated independently from the major activitiesat the 3GeV and 50GeV synchrotron rings. As aresult, we expect to use nearly 100% of the operating

0 20 40 60 80 100 MeVEn

[ENDF]

10 15 20En (MeV)

100Mo(n,2n)99Mo

Fig. 3. Spallation neutron spectrum by a 400MeV proton beam.The 100Mo(n, 2n) cross section (from IAEA (Evaluated NuclearData File)) is inserted.

400 MeV p+Ta

Spallation neutrons

Ta targetProton beam

r [c

m]

Fig. 2. PHITS simulation of spallation neutron emission from the400MeV proton used on a Ta rod of 1.5 cm) # 15 cm long. Theneutron distribution has cylindrical symmetry around the beam.

RCNP/AVF

RCNP/Ring

J-PARC/LINAC

10-1

100

101

10-4

10-3

10-2

102

101 102 103 104

n/p

Sn

Ep(MeV)

SnPb, TaAlCu, FeC

Pb, Ta

Fig. 1. Number of emitted neutrons per single beam proton (n/p)vs. proton energy (Ep), by K. Tesch from Ref. 6.

Towards future self-sufficient supply of the 99Mo-99mTc isotopesNo. 10] 415

time of the injector LINAC. We also expect thatJ-PARC can operate for 50 weeks over one year,and that the parasitic beam time for 10 hours ofirradiation will be scheduled three times a week.Then, the total production time would be (52 week #

3 # 10 hr) F 156 # 10 hr over one year. The totalproduction of 99mTc would amount to 150TBq/year.This is about the half of the total amounts of 99mTcsupply (314TBq in 2013, and 326TBq in 2012).8)

Note that the yield estimation given here is based onan experiment using natural Mo with a 100Mo naturalabundance of 9.63%. Using a highly enriched 100Mo(>90%), 99Mo yield is enhanced by almost a factor of10, so that the 99Mo yield will reach to cover the totalJapanese consumption.

4. Chemical separation and purificationof 99Mo-99mTc for 99mTc generation

Any chemical handling of 99Mo-99mTc isotopes atthe production target has to be done under anextremely high radiation level with minimum dis-turbance to the main J-PARC activities.

We use MoO3 powder as the target material. Wecan dissolve it by infusing a 4mol-NaOH solvent afterirradiation. Then, the 99Mo isotopes are transferredfrom the target vessel in the hot area to a carrier ofradioactive liquid located outside of the acceleratorroom.

We built a new chemical apparatus, named ‘Tcgenerator’9) (Fig. 5). Figure 6 shows .-ray spectraobtained both before and after separation throughthe Tc generator.

A solvent-extraction method with MEK (methylethyl keptone) is used for the separation of Tc fromMo. The Tc extracted from Mo was successfully usedfor taking bone scintigrams.10),11)

Test exp.@ RCNP/ring cyclo.

Beam : 400 MeV 35 nA Irradiation :

Estimationfor the J-PARC mission

Beam : 400 MeV, 330µA Irradiation : 10 hours

x 104

x 20

2 x 105

Scale-up

2 GBq/gr

(Feasibility studty @ RCNP)

(Proposal for J-PARC)

20 GBq/gr

(Use of enriched 100Mo target)

0.5 hour

10 kBqnatMo pellets (10 mmφ x 1mm)

kBq/gr

400 MeV 35nA

Proton beam

*

Fig. 4. Results of feasibility test experiments at the RCNP/cyclotron, and an experimental estimation of the 99Mo yields forthe proposed J-PARC mission.

MEK

NaOH aq.

MEK Saline

Aluminumcolumn

Mixer

Exhaust-(I)

MoO3 solution

Exhaust-(II)

99mTc in Saline

Recovery of Mo

SuctionPump

Sprinkler

MonitorMonitor

Fig. 5. ‘Tc generator’ for the chemical separation of 99mTc from aMoO3 target. The MoO3 is desolved in 4nNaOH, and mixed withMethyl ethyl Kepton (MEK) for solvent extraction. Since thefirst product of extraction contains not only 99mTc, but alsoother Tc isopes as well as other elements, it is thrown awayfrom Exhaust-(I). Then, after waiting for about 10 hours for theaccumulation of 99mTc, 2nd and 3rd extractions are repeated toobtain 99mTc untill the 99Mo in the NaOH aqueous solutiondecays. In the case an enriched 100Mo is used for 99Moproduction, the residue of 100Mo is recovered for later use.

Eγ (keV)

coun

ts

(B)

(A)

104

103

102

101

100

105

104

103

102

101

100

coun

ts

140.

4 ke

V, 9

9mTc

14

0.4

keV,

99m

Tc

Eγ (keV)

1,250 0 250 500 750 1,000

0 250 500 750 1,000 1,250

Fig. 6. Performance of chemical separation and purificationthrough the Tc-generator is monitored by .-ray measurements.Here is an example of .-ray measurements; (A) is before and (B)is after the chemical process passing through the Tc generator.

K. NAKAI et al. [Vol. 90,416

The (MEK) extraction is carried out in twostages:(I) A NaOH solution of the Mo target includes

99mTc together with any impurities as well asother Tc isotopes. Those are extracted in thefirst extraction after production, and the MEKsolution is thrown away.

(II) After waiting for about the half-life necessaryfor building up 99mTc in the NaOH solution, asecond (MEK) extraction generates 99mTc inthe MEK solution exclusively. Then, the 99mTcare further purified by passing through analuminum clomn. This process (II) is repeatedseveral times with intervals of about the half-lifeof 99mTc, until the 99Mo is phased out by decay.In order to examine the performance of the

99mTc produced by (n, 2n) reaction on a Mo target,we compared the quality of the 99mTc samples usingthe present 99mTc source from Mo target with thatusing the conventional commercial source separated

from fission products.12) The latter was made byadding commercially available 99mTc (60MBq) into asolution of natMoO3 (40 g) dissolved in NaOH (4molin 120ml). The 99mTc isotope was extracted with15ml of MEK from a solution containing a macroamount of natural Mo. After the evaporation ofMEK, the dried sample was dissolved in a few ml ofsaline, and the solution was purified by passingthrough a neutral aluminum column to remove anypossible residue of Mo. The amounts of impurities,and the extraction efficiency, etc. were measured byusing inductivity coupled plasma mass spectroscopy(ICP-MS) and .-ray spectroscopy with a Ge detector.The yield of 99mTc was 75–90%. The impurities of Moand Al were less than 10 ppb.

The labeling efficiency of 99mTc-MDP was higherthan 99%. All of these numbers were found to satisfythe requirement of USP (United Statemacs Phar-opeia). The requirement is to keep the impurity atless than 0.01% of the 99mTc.18)

TcGenerators

Liquid RI Bottle

Mo/NaOH solvent

4M NaOH

Hospitals To hot Lab’s

Remote transfer system

Remote handling system

Pb-Bi target

ADS target

Proton Beam J-PARC rings

ADS/TEF-T

ADS target

3GeV-50GeV Rings

99Mo Production TargetMoO3 target

J-PARC injector

Fig. 7. Proposed layout at the J-PARC injector LINAC. The proton beam line for the ADS/TEF-T project is used so that producedneutrons are used parasitically. The MoO3 target is used, which is soluble in 4nNaOH, so that any hot isotopes in the solution can betransferred to a liquid RI bottle outside the accelerator room. Chemical process for separation and purification can be done in localhot-laboratories.

Towards future self-sufficient supply of the 99Mo-99mTc isotopesNo. 10] 417

5. Design and planning of the neutron sourceat the J-PARC/TEF-T facility

We propose a parasitic use of spallation neutronsfrom a target of the 400MeV proton beam in theADS/TEF-T (Accelerator-Driven System/Transmu-tation Experimental Facility-T) beam line withminimum disturbance. Figure 7 shows a preliminaryproposal of a layout for 99Mo-99mTc production,which must be a subject to be improved in practicaluse. The parasitic use of the beam was emphasizedbecause a radioisotope production for medical userequires a stable supply independently of otheractivities. Further detailed design work for construc-tion must be completed in collaboration with J-PARC staff members.

6. Test experiments at the RCNP AVF cyclotronto produce 99Mo isotopes through the (p, pn)

reaction with a 80MeV proton beam

When we had completed the feasibility studiesdiscussed in the previous sections (Sections 2 to 4),and had designed the preliminary scheme discussedin Section 5, we learned that the ADS/TEF-Tproject might take more time than we had expected.We started to explore other possibilities of usinga proton beam with the RCNP AVF (AzimuthallyVarying Field) cyclotron.

Shown in Fig. 8 is the excitation function of the99Mo production through the (p, pn) reaction.

We studied the contributions of the backgroundreactions, and concluded that the optimum beamenergy would be 50 to 80MeV. Although the thicktarget yield increases at higher energy, it is by notmore than 100MeV because of background reactions,such as (p, p2n), (p, p3n), increase.

The 80MeV 1µA proton beam from the AVF-cyclotron was used to bombard a Mo pellet of10mmH, 8.6mm thick (the proton range is8.55mm) to test the 99Mo yield through the (p, pn)reaction. The experimentally obtained 99Mo yieldwas 40MBq/µA/hour. With a 10 hours bombard-ment of a 10 µA proton beam, we can produce 4GBq99Mo isotopes that are sufficient to satisfy the weeklydemand of Osaka University hospital.

7. Test of the direct production of 99mTcvia the Mo(p, 2n) reaction with a 20-MeVproton beam from the RCNP cyclotron

The direct production of 99mTc isotopes via the100Mo(p, 2n) reaction was beyond our scope when westarted the present project. We thought that the half-

life of 99mTc (T1/2 F 6 hours) is too short to make adelivering system to cover a wide area. However, wenoticed that about 50 PET cyclotrons (Ep F 18 or20MeV) are in operation at various locations inJapan to produce isotopes for PET (see red marksin Fig. 9). Each PET cyclotron can produce 99mTcisotopes for in-hospital use.

In order to test the feasibility of the method usingthe 20MeV PET cyclotron for the direct productionof 99mTc isotopes via the Mo(p, 2n) reaction, webombarded a 20MeV 50nA proton beam on a natural

100Mo(p,pn)99Mo

Cro

ss S

ectio

n (m

b)

Lagunus-Solar

(a)

(b)

Cro

ss S

ectio

n (m

b)

Ep (MeV)

o

Theoretical calc.

S. Chiba

Experiments

Fig. 8. Excitation functions of (a) 100Mo(p, pn)99Mo, and (b)100Mo(p, 2n)99mTc reactions. Experimental data from Refs. 14to 17 are plotted.

K. NAKAI et al. [Vol. 90,418

MoO3 pellet target having a thickness of 0.4 g/cm2.Although the irradiation time was only 10min, wewere able to obtain 99mTc of about 5.6 # 104Bq,which led us to conclude that the 99mTc productionyield is 21MBq/µA/hour (at EOB).

The direct production of 99mTc isotopes throughthe 100Mo(p, 2n) reaction using a medical cyclotronhas been investigated since the early 1970’s13) as analternative candidate of the HEU nuclear reactors.

Measurements of the excitation function ofthe (p, 2n) reaction have been reported by threegroups.15)–17) Although the absolute cross sections arenot quite in good agreement, their proton energydependences are similar, showing a broad peak from15 to 20MeV (see Fig. 8(b)).

We compared our data of yield measurementswith the calculated yield by integrating theirexcitation data. Our data were in agreement witha calculation based on data obtained by Scholtenet al.15)

We estimated that by using a 1 µA proton beamon a 96% enriched 100Mo target with a thickness of0.5 g/cm2 for 10 hours, the yield of 99mTc isotopeswould be 3.5GBq. This amount should be sufficientfor typical hospitals. Through the test experimentwith only 10minutes of proton bombardment on anatural Mo target, we concluded that PET cyclo-trons are useful for direct 99mTc production. How-ever, the .-ray spectra showed not only the 99mTcisotope, but also many .-rays from other Tc isotopes(Fig. 10). The Tc isotope contaminations were 93Tc(T1/2 F 2.8 h), 94Tc (T1/2 F 4.9 h), 95Tc (T1/2 F 20 h)and 96Tc (T1/2 F 4.3 d). Those are difficult toseparate through chemical processes. Obviously, we

need to use highly enriched 100Mo (higher than99.5%).18) In order to reduce the production cost,we started to design a new target system for multipleuse of the expensive 100Mo.

8. Summary of feasibility research at RCNP,and concluding remarks

Through the series of RCNP experimentsdiscussed above concerning the feasibility study ofthe 99Mo-96mTc production by the J-PARC injectorbeam, we were able to show that sufficient amountsof 99Mo isotopes could be produced to cover the totalJapanese consumption. Through this work, we areconvinced that the method of producing 99mTcisotopes from a Mo target by the accelerator is gooddespite the fact that the specific activity of 99Mo isvery low. It makes a contrast to the method hithertowell established for Mo chemical separation fromfission products generated in nuclear reactors usingenriched 235U fuel.

Hence, the alternative work would also contrib-ute to reduce the use of enriched 235U fuel.

In Table 2, we summarize our efforts in threescenarios.

We established a Japanese style solution usingthe world top-level high-power accelerator facility,J-PARC. Through the feasibility study using the

Fig. 9. Distribution of low-energy cyclotrons constructed byJapanese SHI (Sumitomo Heavy Industries). Among them, thered marks indicate those that are usable for the direct generationof 99mTc.

0 500 1000 15000 E (keV)C

ount

s

Counts

500 1000 15000 E (keV)

(A)

(B)

99mTc Background ATc Isotopes ( A = 93, 94, 95, 96 )

β+

Fig. 10. Gamma-ray spectra from the 20MeV proton beam on aMo target, taken 10 hours after EOB. The upper spectrum (A) iswith a natural target. The lower one (B) is with a 95% enriched100Mo target and after the chemical process passing through the‘Tc generator’. All peaks in the spectrum (B) were assigned to begamma-rays from Tc isotopes.

Towards future self-sufficient supply of the 99Mo-99mTc isotopesNo. 10] 419

400MeV proton beam from the RCNP/RING-cyclotron, it has been shown that a sufficient amountof 99Mo can be produced at the J-PARC TEF-Tbeam line.

We realized, however, that even though the totalamount of the isotope production is sufficient, therestill remain serious difficulties. For instance, after weachieved full confidence about 99Mo-99mTc produc-tion using the J-PARC, a serious question has arisen.The question is: “what can we do during the periodwhile the J-PARC is not in operation?” The mostimportant factor in serving such medical radioactiveisotopes, like 99Mo, is stable supply. The solution forthe requirement to assure stable supply of isotopes isto have a plural number of production sources.

Among the three scenarios in Table 2, whilescenario (1) is a scheme of global scope, scenario (3)would work in domestic hospitals.

99Mo isotope production at the J-PARC(Scenario (1)). In order to respond to the world-wide crisis of the 99Mo isotope supply with accel-erators in lieu of nuclear reactors, the high-energy,high-intensity accelerator, J-PARC is the mostsuitable facility. Indeed, we have shown throughexperiments at RCNP that a sufficient amount of99Mo isotope production is feasible at J-PARC usingthe spallation neutrons. Since we are considering touse the ADS/TEF-T beam line, we have to wait afew more years for the TEF-T facility.

99mTc direct production at the PET cyclo-trons (Scenario (3)). We learned that in Japanthere exist 50 PET cyclotrons that cover the bestenergy for the direct production of the 99mTc isotope.A series of test experiments at the RCNP cyclotronhave shown the feasibility of direct production. Wethought this to be most promising and practical,being an exclusive medical project.

We found, however, the following two weakpoints: (1) An expensive enriched 100Mo target hasto be used; otherwise, contaminations due to otherTc isotopes can not be separated. (2) In the case ofan emergency, the production of the 99mTc isotopetakes at least a couple of hours for preparation beforean examination. Therefore, the conventional Mogeneration must be kept, and we must continueefforts towards a self-sufficient supply of the 99Moisotopes in parallel.

The 99Mo isotope production network(Scenario (2)). As mentioned in Section 6, besideJ-PARC, we have powerful cyclotrons that accelerateproton beams with an intensity of 100 to 300 µA, andwith an energy of up to 70 or 80MeV. Thosecyclotrons in Japan are all constructed by SHI(Sumitomo Heavy Industry) at Sendai (CYRIC/Tohoku U.), Takasaki (JAEA), and Chiba (NIRS).If these machines provide 200 µA beam on 90%enriched 100Mo targets for 10 hours, each machinecould produce 400GBq 99Mo. Total amounts of

Table 2. Summary of feasible experiments and future prospect

Scenario(1) [Section-3, 4, 5] Scenario(2) [Section-6] Scenario(3) [Section-7]

Production of 99Mo (for Milking) Production of 99Mo (for Milking) Direct Production of 99mTc100Mo(n, 2n)99Mo with spallation neutron 100Mo(p, pn)99Mo 100Mo(p, 2n)99mTc

Feasibility studies at RCNP

Beam proton 400MeV, 35 nA proton 80MeV, 1µA proton; 20MeV, 50 nA

Target natural Mo natural Mo 96% enriched 100Mo

Yield 10 kBq/g/0.5 h 40MBq/µA/h 21MBq/µA/h

Proposal for production at any Japanese accelerator

Scenario(1) Scenario(2) Scenario(3)

Facility J-PARC, ADC/TEF-T (parasitic use) Existing cyclotrons PET cyclotrons

Beam proton; 400MeV, 330 µA (Sendai, Takasaki, Saitama,

Chiba, Osaka, *)

proton; 15–20MeV, 100 µA

Target natural Mo >99.% enriched 100Mo

Yield

2GBq/g/10h

F 1TBq/500 g/10 h

F 150TBq/year (52week:3times/week) [Local support for emergency]

3.5GBq/µA/10 h

F 350GBq/100µA/10 h

e.g. Osaka-U. Hospital

Target >90% enriched 100Mo natural Mo

Yield 1,500TBq/year 94GBq/10 µA/10 h

Demand [Japanese consumption 9 350TBq/year] [3.7GBq/week]

K. NAKAI et al. [Vol. 90,420

3 # 0.4 F 1.2TBq of 99Mo/day are expected to beproduced. If the production could be continued for 54weeks in total during each year, the yield of 65TBq99Mo isotopes is available. This amount is sufficientto cover the 99Tc direct production program at thePET cyclotrons (discussed in Scenario (3)) to estab-lish a self-sufficient supply. We will have to startnegotiation with the nuclear physics community.

The Tc-generator. In all of the cases using the(n, 2n), (n, .), (., n), (p, pn) and (p, 2n) reactions on aMo target, the ‘Tc generator’ discussed in Section 4 isuseful for the separation of 99mTc from 99Mo isotopesproduced with very low specific activities. The newmethod has overcome the difficulty in the chemicalseparation of the 99Mo radioactive isotopes. It is alsocontributing greatly to stop using the highly enriched235U (HEU).

Acknowledgement

The present work was supported by the Re-search Center for Nuclear Physics (RCNP) OsakaUniversity. We are indebted to Director T. Nakanoand supporting staffs of RCNP. We owe thanks toDr. M. Fujiwara for his careful and critical readingof the present paper. We express many thanks to Dr.I. Tanihata, for continuous encouragement and muchadvice. This work was supported by a Grant-in-AidScientific Research (A) (Number 24241030).

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(Received Aug. 5, 2014; accepted Oct. 11, 2014)

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