Feasibility studies towards future self-sufficient supply of the ⁹⁹Mo-^99mTc isotopes with Japanese accelerators

Abstract

In order to establish a self-sufficient supply of ^99mTc, we studied feasibilities to produce its parent nucleus, ⁹⁹Mo, using Japanese accelerators. The daughter nucleus, ^99mTc, is indispensable for medical diagnosis. ⁹⁹Mo has so far been imported from abroad, which is separated from fission products generated in nuclear reactors using enriched ²³⁵U fuel. We investigated ^99mTc production 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 E_p = 50–80 MeV proton at the RCNP cyclotron; (3) ^99mTc direct production with a 20 MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for a scheme on a global scale, scenario (2) works in a local area, and both cases take a long time for negotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for ^99mTc production. We here consider both the advantages and disadvantages among the three scenarios by taking account of the Japanese accelerator situation.

1. Introduction

The radioisotope ^99mTc has long been used for medical diagnostic imaging with the SPECT (Single Photon Emission Computed Tomography) in many hospitals and medical facilities (as many as 1,200). Throughout the long history of radio-medical applications, various chemicals labeled by ^99mTc radioactive isotopes have been developed for medical examination¹⁾ (e.g. blood flow, bone metastasis, etc.; see Table 1).

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

The isotope supply in Japan is mostly from abroad, which may possibly have catastrophic impacts on medical activities when some difficulties might occur concerning the import of ⁹⁹Mo isotopes from abroad in the future. In this paper, we discuss the feasibility for the self-sufficient supply of the ^99mTc isotope in Japan.

The short half-life of ^99mTc (T_1/2 = 6.02 hr) makes a convenient delivering system impossible. However, the ^99mTc isotope is generated through the radioactive decay of ⁹⁹Mo (T_1/2 = 66.0 hr), which can be easily transported over long distances to hospitals.

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

Since the present ⁹⁹Mo production scheme using HEU violates the regulations of PTBT and NPT, we need to develop alternative methods.³⁾ Together with world-wide efforts, new methods to produce the ⁹⁹Mo isotopes have been explored and proposed using Japanese accelerator facilities through photonuclear reactions (γ, n),⁴⁾ neutron-induced reactions (n, 2n)⁵⁾ and (n, γ), as well as proton-incident reactions (p, pn) and (p, 2n).

We started feasibility tests in generating neutrons⁶⁾ from the high-energy, high-intensity proton beam of the injector LINAC (Linear Accelerator) of J-PARC (Japan-Proton Accelerator Research Complex). In this paper, we report on a series of feasibility-test experiments at the Ring-Cyclotron facility of RCNP (Research Center of Nuclear Physics). While the J-PARC/injector LINAC could provide a 400 MeV, 300 µA beam, a proton beam of 400 MeV, 1 µA is available at the RCNP/Ring-Cyclotron. The latter has been a nice playground to test the basic ideas and various feasibilities because of easier access and convenience for experimental designs. We also studied the possibilities of using lower energy proton beams for ⁹⁹Mo production as well as ^99mTc direct production by using the AVF (Azimuthally Varying Field) cyclotron.

2. Production of ⁹⁹Mo isotopes with spallation neutrons

In nuclear reactions using projectiles above 100 MeV/nucleon, the collision speed becomes faster than the nucleon Fermi motion in nuclei, or above the sound velocity of nuclear matter. Therefore, the neutron yield increases dramatically through the spallation process (see Fig. 1). We expect to increase the ⁹⁹Mo yield via the ¹⁰⁰Mo(n, 2n)⁹⁹Mo reaction. For producing medical isotopes, however, the specific activity is an additional factor to optimize the proton energy. We used a 400 MeV proton beam on a heavy-metal target to produce spallation neutrons, so that the ⁹⁹Mo isotope would be produced via the ¹⁰⁰Mo(n, 2n) reaction on a natural Mo target. A heavy-metal Mo, Ta, or W target was used to generate fast neutrons by the (n, xn) reaction. We used the Monte-Carlo program ‘PHITS’⁷⁾ (Particle and Heavy Ion Transport code System) for designing the experiments. An example of the PHITS simulation for neutron emission from 400 MeV protons on a thick Ta target is shown in Fig. 2. In contrast to the forward-enhanced distribution at low incident energies, lower than 100 MeV, spallation neutrons are emitted sideways. Hence, a cylindrical target configuration is favorable when using neutrons for the ¹⁰⁰Mo(n, 2n) reaction. Figure 3 shows a typical spectrum of spallation neutrons. In this figure, the production cross section for the ¹⁰⁰Mo(n, 2n)⁹⁹Mo reaction is inserted. The neutron yields decrease monotonically with increasing the neutron energy. Thus, the overlaps between the neutron yields and the ¹⁰⁰Mo(n, 2n)⁹⁹Mo cross section is not ideally good. However, there was almost no way to change the neutron spectrum shape. The high-energy proton beam allows us to use a thick target, as long as 15 cm.

Fig. 1.

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

Fig. 2.

PHITS simulation of spallation neutron emission from the 400 MeV proton used on a Ta rod of 1.5 cmΦ × 15 cm long. The neutron distribution has cylindrical symmetry around the beam.

Fig. 3.

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

3. Feasibility studies at RCNP for proposing the project at J-PARC

In order to propose a ⁹⁹Mo-^99mTc production project at J-PARC, we carried out a series of experiments using the 400 MeV proton beam at the Ring cyclotron of RCNP. With the target configuration set to use the cylindrically distributed spallation neutrons, as shown in Fig. 2, experiments were carried out to test ⁹⁹Mo production. A 400 MeV 35 nA proton beam was incident on a neutron-production target of a natural Mo rod with 15 mm diameter and 150 mm length. The range of 400 MeV protons in a metallic Mo target was calculated to be 128 mm. Neutrons were emitted sideways along the beam axis in the Mo target. For determining the ⁹⁹Mo production rate, we used natural Mo pellets of 10 mm diameter and 1 mm thickness set along the side 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, after cooling any background activities, γ-ray analyses were performed to determine the yield. The result showed that the ⁹⁹Mo yield obtained by bombarding the 400 MeV 35 nA proton beam for 0.5 hr on a natural Mo target was at least 10 kBq/g. As shown in Fig. 4, the ⁹⁹Mo yield expected in the case of J-PARC using the 400 MeV 330 µA proton beam for 10 hr is given by   

\begin{align*} &\text{(10$\,$kBq/g)}\times\text{(330$\,\mu$A/35$\,$nA)(10$\,$hr/0.5$\,$hr)} \\ &\quad\sim \text{2$\,$GBq/g/10$\,$hr} \end{align*}

If a 500 g natural Mo target is used, we expect to obtain 1 TBq/10 hr. We propose to add this function to the J-PARC/injector-LINAC as a parasite job to be operated independently from the major activities at the 3 GeV and 50 GeV synchrotron rings. As a result, we expect to use nearly 100% of the operating time of the injector LINAC. We also expect that J-PARC can operate for 50 weeks over one year, and that the parasitic beam time for 10 hours of irradiation will be scheduled three times a week. Then, the total production time would be (52 week × 3 × 10 hr) = 156 × 10 hr over one year. The total production of ^99mTc would amount to 150 TBq/year. This is about the half of the total amounts of ^99mTc supply (314 TBq in 2013, and 326 TBq in 2012).⁸⁾ Note that the yield estimation given here is based on an experiment using natural Mo with a ¹⁰⁰Mo natural abundance of 9.63%. Using a highly enriched ¹⁰⁰Mo (>90%), ⁹⁹Mo yield is enhanced by almost a factor of 10, so that the ⁹⁹Mo yield will reach to cover the total Japanese consumption.

Fig. 4.

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

4. Chemical separation and purification of ⁹⁹Mo-^99mTc for ^99mTc generation

Any chemical handling of ⁹⁹Mo-^99mTc isotopes at the production target has to be done under an extremely high radiation level with minimum disturbance to the main J-PARC activities.

We use MoO₃ powder as the target material. We can dissolve it by infusing a 4 mol-NaOH solvent after irradiation. Then, the ⁹⁹Mo isotopes are transferred from the target vessel in the hot area to a carrier of radioactive liquid located outside of the accelerator room.

We built a new chemical apparatus, named ‘Tc generator’⁹⁾ (Fig. 5). Figure 6 shows γ-ray spectra obtained both before and after separation through the Tc generator.

Fig. 5.

‘Tc generator’ for the chemical separation of ^99mTc from a MoO₃ target. The MoO₃ is desolved in 4nNaOH, and mixed with Methyl ethyl Kepton (MEK) for solvent extraction. Since the first product of extraction contains not only ^99mTc, but also other Tc isopes as well as other elements, it is thrown away from Exhaust-(I). Then, after waiting for about 10 hours for the accumulation of ^99mTc, 2^nd and 3^rd extractions are repeated to obtain ^99mTc untill the ⁹⁹Mo in the NaOH aqueous solution decays. In the case an enriched ¹⁰⁰Mo is used for ⁹⁹Mo production, the residue of ¹⁰⁰Mo is recovered for later use.

Fig. 6.

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

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

The (MEK) extraction is carried out in two stages:

1. (I)   A NaOH solution of the Mo target includes ^99mTc together with any impurities as well as other Tc isotopes. Those are extracted in the first extraction after production, and the MEK solution is thrown away.
2. (II)   After waiting for about the half-life necessary for building up ^99mTc in the NaOH solution, a second (MEK) extraction generates ^99mTc in the MEK solution exclusively. Then, the ^99mTc are further purified by passing through an aluminum clomn. This process (II) is repeated several times with intervals of about the half-life of ^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 using the present ^99mTc source from Mo target with that using the conventional commercial source separated from fission products.¹²⁾ The latter was made by adding commercially available ^99mTc (60 MBq) into a solution of ^natMoO₃ (40 g) dissolved in NaOH (4 mol in 120 ml). The ^99mTc isotope was extracted with 15 ml of MEK from a solution containing a macro amount of natural Mo. After the evaporation of MEK, the dried sample was dissolved in a few ml of saline, and the solution was purified by passing through a neutral aluminum column to remove any possible residue of Mo. The amounts of impurities, and the extraction efficiency, etc. were measured by using inductivity coupled plasma mass spectroscopy (ICP-MS) and γ-ray spectroscopy with a Ge detector. The yield of ^99mTc was 75–90%. The impurities of Mo and Al were less than 10 ppb.

The labeling efficiency of ^99mTc-MDP was higher than 99%. All of these numbers were found to satisfy the requirement of USP (United Statemacs Pharopeia). The requirement is to keep the impurity at less than 0.01% of the ^99mTc.¹⁸⁾

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

We propose a parasitic use of spallation neutrons from a target of the 400 MeV proton beam in the ADS/TEF-T (Accelerator-Driven System/Transmutation Experimental Facility-T) beam line with minimum disturbance. Figure 7 shows a preliminary proposal of a layout for ⁹⁹Mo-^99mTc production, which must be a subject to be improved in practical use. The parasitic use of the beam was emphasized because a radioisotope production for medical use requires a stable supply independently of other activities. Further detailed design work for construction must be completed in collaboration with J-PARC staff members.

Fig. 7.

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

6. Test experiments at the RCNP AVF cyclotron to produce ⁹⁹Mo isotopes through the (p, pn) reaction with a 80 MeV proton beam

When we had completed the feasibility studies discussed in the previous sections (Sections 2 to 4), and had designed the preliminary scheme discussed in Section 5, we learned that the ADS/TEF-T project might take more time than we had expected. We started to explore other possibilities of using a proton beam with the RCNP AVF (Azimuthally Varying Field) cyclotron.

Shown in Fig. 8 is the excitation function of the ⁹⁹Mo production through the (p, pn) reaction.

Fig. 8.

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

We studied the contributions of the background reactions, and concluded that the optimum beam energy would be 50 to 80 MeV. Although the thick target yield increases at higher energy, it is by not more than 100 MeV because of background reactions, such as (p, p2n), (p, p3n), increase.

The 80 MeV 1 µA proton beam from the AVF-cyclotron was used to bombard a Mo pellet of 10 mmφ, 8.6 mm thick (the proton range is 8.55 mm) to test the ⁹⁹Mo yield through the (p, pn) reaction. The experimentally obtained ⁹⁹Mo yield was 40 MBq/µA/hour. With a 10 hours bombardment of a 10 µA proton beam, we can produce 4 GBq ⁹⁹Mo isotopes that are sufficient to satisfy the weekly demand of Osaka University hospital.

7. Test of the direct production of ^99mTc via the Mo(p, 2n) reaction with a 20-MeV proton beam from the RCNP cyclotron

The direct production of ^99mTc isotopes via the ¹⁰⁰Mo(p, 2n) reaction was beyond our scope when we started the present project. We thought that the half-life of ^99mTc (T_1/2 = 6 hours) is too short to make a delivering system to cover a wide area. However, we noticed that about 50 PET cyclotrons (E_p = 18 or 20 MeV) are in operation at various locations in Japan to produce isotopes for PET (see red marks in Fig. 9). Each PET cyclotron can produce ^99mTc isotopes for in-hospital use.

Fig. 9.

Distribution of low-energy cyclotrons constructed by Japanese SHI (Sumitomo Heavy Industries). Among them, the red marks indicate those that are usable for the direct generation of ^99mTc.

In order to test the feasibility of the method using the 20 MeV PET cyclotron for the direct production of ^99mTc isotopes via the Mo(p, 2n) reaction, we bombarded a 20 MeV 50 nA proton beam on a natural MoO₃ pellet target having a thickness of 0.4 g/cm². Although the irradiation time was only 10 min, we were able to obtain ^99mTc of about 5.6 × 10⁴ Bq, which led us to conclude that the ^99mTc production yield is 21 MBq/µA/hour (at EOB).

The direct production of ^99mTc isotopes through the ¹⁰⁰Mo(p, 2n) reaction using a medical cyclotron has been investigated since the early 1970’s¹³⁾ as an alternative candidate of the HEU nuclear reactors.

Measurements of the excitation function of the (p, 2n) reaction have been reported by three groups.^15)–17) Although the absolute cross sections are not quite in good agreement, their proton energy dependences are similar, showing a broad peak from 15 to 20 MeV (see Fig. 8(b)).

We compared our data of yield measurements with the calculated yield by integrating their excitation data. Our data were in agreement with a calculation based on data obtained by Scholten et al.¹⁵⁾

We estimated that by using a 1 µA proton beam on a 96% enriched ¹⁰⁰Mo target with a thickness of 0.5 g/cm² for 10 hours, the yield of ^99mTc isotopes would be 3.5 GBq. This amount should be sufficient for typical hospitals. Through the test experiment with only 10 minutes of proton bombardment on a natural Mo target, we concluded that PET cyclotrons are useful for direct ^99mTc production. However, the γ-ray spectra showed not only the ^99mTc isotope, but also many γ-rays from other Tc isotopes (Fig. 10). The Tc isotope contaminations were ⁹³Tc (T_1/2 = 2.8 h), ⁹⁴Tc (T_1/2 = 4.9 h), ⁹⁵Tc (T_1/2 = 20 h) and ⁹⁶Tc (T_1/2 = 4.3 d). Those are difficult to separate through chemical processes. Obviously, we need to use highly enriched ¹⁰⁰Mo (higher than 99.5%).¹⁸⁾ In order to reduce the production cost, we started to design a new target system for multiple use of the expensive ¹⁰⁰Mo.

Fig. 10.

Gamma-ray spectra from the 20 MeV proton beam on a Mo target, taken 10 hours after EOB. The upper spectrum (A) is with a natural target. The lower one (B) is with a 95% enriched ¹⁰⁰Mo target and after the chemical process passing through the ‘Tc generator’. All peaks in the spectrum (B) were assigned to be gamma-rays from Tc isotopes.

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

Through the series of RCNP experiments discussed above concerning the feasibility study of the ⁹⁹Mo-^96mTc production by the J-PARC injector beam, we were able to show that sufficient amounts of ⁹⁹Mo isotopes could be produced to cover the total Japanese consumption. Through this work, we are convinced that the method of producing ^99mTc isotopes from a Mo target by the accelerator is good despite the fact that the specific activity of ⁹⁹Mo is very low. It makes a contrast to the method hitherto well established for Mo chemical separation from fission products generated in nuclear reactors using enriched ²³⁵U fuel.

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

In Table 2, we summarize our efforts in three scenarios.

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 99mTc
	100Mo(n, 2n)99Mo with spallation neutron	100Mo(p, pn)99Mo	100Mo(p, 2n)99mTc
Feasibility studies at RCNP
Beam	proton 400 MeV, 35 nA	proton 80 MeV, 1 µA	proton; 20 MeV, 50 nA
Target	natural Mo	natural Mo	96% enriched 100Mo
Yield	10 kBq/g/0.5 h	40 MBq/µA/h	21 MBq/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; 400 MeV, 330 µA	(Sendai, Takasaki, Saitama, Chiba, Osaka, ⋯)	proton; 15–20 MeV, 100 µA
Target	natural Mo		>99.% enriched 100Mo
Yield	2 GBq/g/10 h = 1 TBq/500 g/10 h = 150 TBq/year (52week:3times/week)	[Local support for emergency]	3.5 GBq/µA/10 h = 350 GBq/100 µA/10 h
		e.g. Osaka-U. Hospital
Target	>90% enriched 100Mo	natural Mo
Yield	1,500 TBq/year	∼4 GBq/10 µA/10 h
Demand	[Japanese consumption ∼ 350 TBq/year]	[3.7 GBq/week]

We established a Japanese style solution using the world top-level high-power accelerator facility, J-PARC. Through the feasibility study using the 400 MeV proton beam from the RCNP/RING-cyclotron, it has been shown that a sufficient amount of ⁹⁹Mo can be produced at the J-PARC TEF-T beam line.

We realized, however, that even though the total amount of the isotope production is sufficient, there still remain serious difficulties. For instance, after we achieved full confidence about ⁹⁹Mo-^99mTc production using the J-PARC, a serious question has arisen. The question is: “what can we do during the period while the J-PARC is not in operation?” The most important factor in serving such medical radioactive isotopes, like ⁹⁹Mo, is stable supply. The solution for the requirement to assure stable supply of isotopes is to have a plural number of production sources.

Among the three scenarios in Table 2, while scenario (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 accelerators in lieu of nuclear reactors, the high-energy, high-intensity accelerator, J-PARC is the most suitable facility. Indeed, we have shown through experiments at RCNP that a sufficient amount of ⁹⁹Mo isotope production is feasible at J-PARC using the spallation neutrons. Since we are considering to use the ADS/TEF-T beam line, we have to wait a few more years for the TEF-T facility.

^99mTc direct production at the PET cyclotrons (Scenario (3)).

We learned that in Japan there exist 50 PET cyclotrons that cover the best energy for the direct production of the ^99mTc isotope. A series of test experiments at the RCNP cyclotron have shown the feasibility of direct production. We thought this to be most promising and practical, being an exclusive medical project.

We found, however, the following two weak points: (1) An expensive enriched ¹⁰⁰Mo target has to be used; otherwise, contaminations due to other Tc isotopes can not be separated. (2) In the case of an emergency, the production of the ^99mTc isotope takes at least a couple of hours for preparation before an examination. Therefore, the conventional Mo generation must be kept, and we must continue efforts towards a self-sufficient supply of the ⁹⁹Mo isotopes in parallel.

The ⁹⁹Mo isotope production network (Scenario (2)).

As mentioned in Section 6, beside J-PARC, we have powerful cyclotrons that accelerate proton beams with an intensity of 100 to 300 µA, and with an energy of up to 70 or 80 MeV. Those cyclotrons 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 machine could produce 400 GBq ⁹⁹Mo. Total amounts of 3 × 0.4 = 1.2 TBq of ⁹⁹Mo/day are expected to be produced. If the production could be continued for 54 weeks in total during each year, the yield of 65 TBq ⁹⁹Mo isotopes is available. This amount is sufficient to cover the ⁹⁹Tc direct production program at the PET cyclotrons (discussed in Scenario (3)) to establish a self-sufficient supply. We will have to start negotiation with the nuclear physics community.

The Tc-generator.

In all of the cases using the (n, 2n), (n, γ), (γ, n), (p, pn) and (p, 2n) reactions on a Mo target, the ‘Tc generator’ discussed in Section 4 is useful for the separation of ^99mTc from ⁹⁹Mo isotopes produced with very low specific activities. The new method has overcome the difficulty in the chemical separation of the ⁹⁹Mo radioactive isotopes. It is also contributing greatly to stop using the highly enriched ²³⁵U (HEU).

Acknowledgement

The present work was supported by the Research Center for Nuclear Physics (RCNP) Osaka University. We are indebted to Director T. Nakano and supporting staffs of RCNP. We owe thanks to Dr. M. Fujiwara for his careful and critical reading of the present paper. We express many thanks to Dr. I. Tanihata, for continuous encouragement and much advice. This work was supported by a Grant-in-Aid Scientific Research (A) (Number 24241030).

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