Proceedings of the 14th Annual Meeting of Particle Accelerator Society of Japan
August 1-3, 2017, Sapporo, Japan

PASJ2017 TUP133

PHOTONUCLEAR PRODUCTION OF SELF-TARGETING MEDICALRADIONUCLIDES USING AN X-BAND ELECTRON LINEAR
ACCELERATOR: A FEASIBILITY STUDY
Jaewoong Jang∗ , Dept. of Bioengineering, University of Tokyo, Bunkyo, Tokyo 113-8656, Japan
Mitsuru Uesaka, Nuclear Professional School, University of Tokyo, Naka, Ibaraki 319-1188, Japan
Masashi Yamamoto, Accuthera Inc., Kawasaki, Kanagawa 215-0033, Japan
Table 1: Decay Characteristics of 54 Mn and 87m Sr

Abstract
Motivated by the 2009–2010 global 99 Mo/99m Tc supply
disruptions, we recently designed an X-band electron linear accelerator intended for 99 Mo production. Further tothis, we examined photonuclear production of radionuclides
which can concentrate in body organs without biomolecules.
Of particular interest are 54 Mn and 87m Sr, which can be produced via 55 Mn(γ,n)54 Mn and 88 Sr(γ,n)87m Sr, respectively.
Here we present their radiopharmaceutical potentials, target
designs, and expected yields.

Physical half-life
Emitting radiation

312.3 d2.8 hECa γ 834.8 keV

ITb γ 388.5 keV

55 Mn(γ,n)54 Mn

88 Sr(γ,n)87m Sr

55 Mn: 100%

88 Sr: 82.6%

MyocardiumBone(99.9%)

Nuclear reaction
Target abundance
Targeting organ

87m Sr(81.9%)

a Electron capture.
b Isomeric transition.

INTRODUCTION
Technetium-99m (99m Tc), with which over 80% of allradiopharmaceutical scans are carried out [1], is generally
obtained through the negatron ( β − ) decay of molybdenum99 (99 Mo). For decades, 99 Mo has been supplied as a fission
product of 235 U [2]. Owing to aging of the involved reactors,
however, this fission-based 99 Mo supply chain has become
fragile, highlighting the need for an alternative 99 Mo production method. 99 Mo production via the 100 Mo photoneutron
reaction is an example, for which we recently designed an
X-band electron linear accelerator (linac) [3, 4]. Thereafter,
in an attempt to extend the range of available medical radionuclides, we studied electron-linac-based production ofmanganese-54 (54 Mn) and strontium-87m (87m Sr), which
we deem potential imaging agents for the heart and bone,respectively.

SELF-TARGETING MEDICALRADIONUCLIDES

are such self-targeting medical radionuclides, of which thedecay properties are given in Table 1 [6].
54 Mn

We are attempting to produce 54 Mn via the 55 Mn photoneutron reaction, or 55 Mn(γ,n)54 Mn; the threshold energy
is known to be 10.2 MeV [6].
Studies [7] have shown that the myocardial uptake of 54 Mn
can be higher than that of 201 Tl, a popular heart imaging
agent. This stems from the fact that mitochondria, in which
manganese is localized, are abundant in the myocardium [7].
As 54 Mn exhibits a relatively long physical half-life Tphy ,it is worth noting that the time during which a radionuclide
stays in a body is not simply dictated by Tphy , but by theeffective half-life Teff :Teff =A radiopharmaceutical is essentially a radiolabeled active
ingredient (AI) designed to be concentrated in a specificbody organ. For instance, when 99m Tc-ECD is administered
to a patient, the ECD is taken up by the brain [5], while the99m Tc provides their location information using its 140.5keV γ-rays. As such, it is mostly the AI that directs its
radiopharmaceutical to the target organ, while the attachedradionuclide is used merely for their detection.
Developing an AI requires, however, a substantial researchbudget and a long period of time. In order to circumvent thisresearch barrier, and to make more radionuclides available
for medicine and research, we investigated radionuclides
which can concentrate in body organs without AIs and canbe produced via photonuclear reactions. 54 Mn and 87m Sr∗ jang@nuclear.jp

54 Mn

Tphy Tbio
Tphy + Tbio

where Tbio represents the biological half-life.
Moreover, reasonable production costs are expected fromthe isotopic abundance of the target material: 55 Mn accounts
for 100% of naturally occurring manganese (nat Mn).
87m Sr87m Sr can be produced via 88 Sr(γ,n)87m Sr, of which thethreshold energy is approximately 11.1 MeV [6].
Belonging to the same group as calcium in the periodic
table, strontium has a great affinity to bone matrix [8]. The
skeletal system can therefore be visualized by 87m Sr.
Remarkable advantages of 87m Sr are its moderate Tphy
and γ-ray energy, shown in Table 1. Affordable production
costs are also expected, as the natural abundance of 88 Sr is
as high as 82.6%.

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August 1-3, 2017, Sapporo, Japan

PASJ2017 TUP133

Eγ,minTable 2: Target Assembly Dimensions
Targetnat W

Parameter(cm)

ShapeRadiusThickness
Lower radiusUpper radius
HeightDisk55 Mn /88 Sr

Truncated
cone

Volume(cm3 )
2.0
0.1
0.5
1.5
3.0

− ln 2 (7Tphy )1 − e Tphy

1.26

≈ 0.992

On the other hand, because 7Tphy of 54 Mn is impracticallylong for target irradiation, t irr for 55 Mn(γ,n)54 Mn was chosen taking into account the time during which the naturaltungsten (nat W) bremsstrahlung converter can withstand thethermal stress.
σ8887mσ55

54Sr(γ,n)ΦMC in 88SrSr

ΦMC in 55Mn

Mn(γ,n) Mn

0.24

10-2

10-3

0.22

Microscopic cross section σ (b)(1)
where Ai (t irr ) is the activity of a radionuclide i during target
irradiation time t irr , λ i is the decay constant of i, Vtar isthe target volume, Ib is the electron beam current, Eγ isthe bremsstrahlung energy, ΦMC (Eγ ) is the bremsstrahlung
fluence obtained by an MC simulation program, and Σ(Eγ )is the macroscopic cross section for producing i.
The target configurations used in the simulation runs are
summarized in Table 2, and illustrated graphically in Fig. 1.
Besides, the beam energy and average current of the X-band
electron linac we designed, found in Ref. [3], were 35 MeV
and 260 µA, respectively. Using these beam parameters, inaddition to Vtar of Table 2 and the photonuclear reaction
cross sections contained in TENDL-2009 [10], we evaluated Eq. (1) for 54 Mn and 87m Sr.

-1

Z Eγ,maxfgAi (t irr ) = 1 − e−λi tirr Vtar Ib
ΦMC (Eγ )Σ(Eγ ) dEγof 54 Mn is as low as 9.248 × 10−5 h-1 . Accordingly, rather
than plotting their yields with respect to irradiation time,
we coplot in Fig. 2 their microscopic cross sections withbremsstrahlung fluences averaged over the respective target
volumes, and tabulate their activities in Table 3. Here t irr for
88 Sr(γ,n)87m Sr was selected considering the time at which
the 87m Sr activity converges to its maximal activity, which
is approximately 7Tphy :-2

We performed Monte Carlo (MC) simulations using
PHITS version 2.88 [9], for evaluating [4]As implied by the exponential term, however, the production rates of the two radionuclides differ to a great extent: thedecay constant λ = Tlnphy2 of 87m Sr is 0.248 h-1 , whereas that

10.21

0.20
0.18
0.16
0.14
10-4

0.12
0.10
0.08

10-50.060.040.02

10-6350.00
51015202530

Bremsstrahlung fluence ΦMC (cm electron )SIMULATION-BASED YIELDESTIMATION

Bremsstrahlung energy Eγ (MeV)210−2x (cm)

10−3

10−4

010−5nat55

W10−6Mn

10−7−2

Bremsstrahlung fluence (cm-2 electron-1)

10−1

Figure 2: Microscopic cross sections contained in TENDL2009 and volume-averaged bremsstrahlung fluences calculated at Ee = 35 MeV.
Table 3: Evaluation Results of Eq. (1)Product54 Mn87m Sr

10−8−1012z (cm)34calculated by PHITS 2.88
plotted by ANGEL 4.35

Figure 1: Bremsstrahlung tracks in the nat W-55 Mn target
assembly simulated at electron beam energy Ee = 35 MeV.

t irr to saturation activity(∼ 7Tphy )t irr

Ai (t irr )2186.1 d
19.6 h72 h
18 h

170.8 GBq
14.5 TBq

Although the evaluated 54 Mn and 87m Sr activities are theones before chemical processing and delivery to end users,
considering the activity loss factors of 99 Mo/99m Tc supply
chain and average dose of commercial radiopharmaceuticals,
we find the resulting 54 Mn and 87m Sr activities fairly high.
Utilizing the compactness of the designed X-band electron
linac, then, sufficient quantities of these self-targeting radionuclides can be supplied with satisfactory accessibility.

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Proceedings of the 14th Annual Meeting of Particle Accelerator Society of Japan
August 1-3, 2017, Sapporo, Japan

PASJ2017 TUP133

99 Mo/99m Tc market demand and production capacity projec-POST-IRRADIATION CHEMICALPROCESSING
Following its production, a medical radionuclide should
be chemically processed to meet pharmacopeial standards.
Examples include pH adjustment and additive addition, andchemical separation if the radionuclide in question is obtained through its parent. Furthermore, as mentioned earlier,almost all medical radionuclides are compounded with organic molecules to form radiopharmaceuticals. In contrast,
as 54 Mn and 87m Sr are designed to be self-targeting, and canbe produced directly from photonuclear reactions, simpler
chemical processing is expected.

SUMMARY
Conventional radiopharmaceuticals are a mixture of
biomolecules and radionuclides, the former of which makeradiopharmaceutical development demanding. In a bid to bypass this involvement of biomolecules or AIs, and to extend
the range of electron-linac-producible medical radionuclides,
we examined the radiopharmaceutical potentials, photonuclear production methods, and yields of 54 Mn and 87m Sr.
We expect that using the X-band electron linac we recently
designed can enable producing these self-targeting medical radionuclides in close proximity to radiopharmacies orlaboratories.

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[2] National Academies of Sciences, Engineering, and Medicine,
Molybdenum-99 for medical imaging. WA, USA: National
Academies Press, 2016.
[3] J. Jang, M. Yamamoto, and M. Uesaka, “Development of acompact X-band electron linac for production of Mo-99/Tc-99m”, in Proc. 7th Int. Particle Accelerator Conf.
(IPAC’16), Busan, Korea, May 2016, paper TUPOY007, pp.
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[4] J. Jang, M. Yamamoto, and M. Uesaka, “Design of a compact
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[5] S. R. Cherry, J. A. Sorenson, and M. E. Phelps, Physics in
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[6] S. Y. F. Chu, L. P. Ekström, and R. B. Firestone; http://
nucleardata.nuclear.lu.se/toi/[7] D. M. Chauncey, Jr. et al., “Tissue distribution studies withradioactive manganese: a potential agent for myocardial imaging”, J. Nucl. Med., vol. 18, no. 9, pp. 933–936, Sept. 1977.
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[10] A J. Koning and D. Rochman, “Modern nuclear data evaluation with the TALYS code system”, Nucl. Data Sheets, vol.
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