1. health and fitness
2. therapy

A potential selective radiotherapy for ocular melanoma
by sulfur neutron capture
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I. Porras , P.L. Esquinas , M.G. Feldmann , J. Praena
1
and F. Arias de Saavedra
1
Departamento de F´ısica At´omica, Molecular y Nuclear, Universidad de Granada, Granada, Spain
2
Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.
3
Department of Ophthalmology, Park Nicollet Clinic, St. Louis Park, USA.
4
Departamento de F´ısica At´omica, Molecular y Nuclear, Universidad de Sevilla, Seville, Spain
5
Centro Nacional de Aceleradores (CNA), Seville, Spain
Figure 4 shows the angular distribution of the kerma rate seen
from the center of the eye and being the angle cero the center
of the tumor. It shows that the main contribution to the kerma
rate corresponds to small angles (tumor zone).
radiation dose in healthy tissue.
Introduction
Results
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Choroidal melanoma is a cancer resistant to chemotherapy
and difficult for radiotherapy as the tumor is close to very
sensitive organs to radiation.
The collaborative ocular melanoma study (COMS) [1] recommends two treatments:
Kerma Rate (Gy/min)
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Enucleation (surgical removal of the eye).
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Brachytherapy disk implants with seeds of 125I, a low energy photon emitter. Its success imposes a important gradient dose between the tumor and the surrounding healthy
tissues. And when the minimal radiation dose required for
tumor destruction (85 Gy) is used, adverse effects may occur [2], such as retinopathy or optic neuropathy.
Figure 1 shows a 2-D color map of the average total dose
deposited on different elements after the eye has been irradiated with a 2 cm diameter, 13.5 keV monoenergetic neutron A realistic possibility for producing quasi-monoenergetic
beam, with a flux of 9 · 1011 neutrons/cm2 for two different 13.45 keV-neutron beam is based on the proton beam coltumor locations.
lision on a lithium target via the 7Li(p,n)7Be reaction near the
Due to higher concentration of 33S in tumor, the sulfur iso- threshold, because the resulting neutron spectrum depends on
tope captures a fraction of the primary neutrons, alpha par- the proton energy and emission angle [8].
ticles are emitted and a high biologically effective dose is High intensity accelerators (10-100 mA of current) for neutron production are in project for BNCT applications [9]. We
delivered locally in the tumor.
have estimated this with the code NeuSDesc [10]. Proton
33
The S tumor-to-normal tissue ratio allows a large dose
beam of 1.9 MeV impinging on a LiF target predicts, at an
gradient, sparing radiosensitive areas such as, lens, cornea
angle of 52o, a neutron fluence of 1.6 108 neutrons/(s cm2)
and optic nerve preventing induced radiation complicamA with a sharp spectrum of energy centered close to the
tions.
resonance peak of 13.45 keV. We have obtained consistent
When the eye is voxeled in the right case in Figure 1, we get: number for this situation using Lee’s more detailed analysis
[8]. This is an interesting possibility to explore when these
accelerators become available.
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Porras showed that the presence of 33S in tumor cells would
produce a sharp enhancement of the radiation dose delivered
by a source of neutrons of an appropriate low energy (13.45
keV), by means of a resonance capture reaction [3]. 33S is a
stable isotope and reacts with neutrons producing the emission of an alpha particle with a huge energy (3.5 MeV) in
a very small range (of the order of a cell size) with a much
higher biological effectiveness than photons.
Sulfur may be absorbed selectively by tumors via the enhanced metabolism of the malignant cells. A potential carrier
is 2-thiouracil, which binds to melanin precursors, and not
to preformed melanin, and so it concentrates selectively in
melanoma in mice, with tumor-to-normal tissue ratios greater
than 50 [4]. Other potential structures are recently synthesized sulfur nanoparticles [5].
The outcome of this therapy cannot be presently studied by
direct experimentation because there are no known neutron
sources of this type available.
The aim of this work is to study, by Monte Carlo simula- More detailed results, in the left case in Figure 1, are shown
tions, the viability of this kind of therapy. We have studied in Figures 3 and 4 where the total kerma rate deposited is
the mimimum flux of neutrons needed to provide the radi- decomposed in different contributions according to its orign:
ational dose that garantees the tumor destruction. We have
the fast neutrons
discussed if this technique also provides the gradient of dose
the photons
needed to avoid adverse effects in the sorrounding organs.
the S33
After that, we have chosen the conditions needed in the rethe total contribution
action 7Li(p,n)7 to provide almost monoenergetic neutrons of
13.45 keV. Finally we present our conclusions.
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Angle (degrees)
40
60
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Finantial support is acknowledged to Biotic Granada Campus for International Excellence (CEI2014-PBS64), to Feder and Spanish MINECO
(FIS2012-39612-C02-01) and to Junta de Andaluc´ıa (P11-FQM-8229).
References
[1] http://www.jhu.edu/wctb/coms/
[2] I. Puusaari, J. Heikkonen and T. Kivel, Effect of Radiation
Dose on Ocular Complications after Iodine Brachytherapy
for Lager Uveal Melanoma: Empirical Data and Simulation of Collimation Plaques. Invest. Ophthalmol. Vis. Sci. 45,
3425-34 (2004).
[3] I. Porras, Enhancement of neutron radiation dose by the addition of sulphur-33 atoms. Phys. Med. Biol. 53, L1-9 (2008);
Sulfur-33 nanoparticles: a Monte Carlo study of their potential as neutron capturers for enhancing boron neutron capture
therapy of cancer. Appl. Radiat. Isot. 69, 1838-41 (2011).
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Method
Kerma Rate (Gy/min)
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[4] J.A. Coderre, S. Packer, R.G. Fairchild, D. Greenberg, B.
Laster, P. Micca and I. Fand, Iodothiouracil as a melanoma
localizing agent. J. Nucl. Med. 27, 1157-64 (1986).
[5] R. Tenne, Inorganic nanotubes and fullerene-like nanoparticles. Nature Nanotechnology 1, 103-11 (2006).
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[6] D.B. Pelowitz, MCNPXT M Users Manual, Version 2.5.0.
Publication LACP-05-0369, Los Alamos National Laboratory, Los Alamos, NM (2005).
Here, we have evaluated our Monte Carlo simulations using
the MCNPX code [6], the radiation dose components in an
[7] H. Yoriyaz, A. Sanchez and A. dos Santos, A new human eye
eye model inspired by Yoriyaz et al. [7]. This eye model,
model for ophthalmic brachytherapy dosimetry. Radiat. Prot.
shown in Figure 1, includes regions of interest such as lens,
Dosimetry 115, 316-9 (2005).
macula and optic nerve and a dome-shaped choroidal tumor. It is common to both figures that:
[8] C.L. Lee and X.-L. Zhou, Thick target neutron yields for the
7Li(p,n)7Be reaction near threshold. Nucl. Inst. and Meth. in
We will show results with this tumor located in different poContributions from the photons and the termic neutrons are
sitions.
Phys. Res. B 152, 1-11 (1999).
not
relevant
In our analysis, we have supposed a 33S concentration of 10
[9] S. Liberman et al. eds., New Challenges in Neutron CapMain contributions inside the tumor come from the fast
ture Therapy: Proceedings of 14th International Congress on
mg/g in the tumor, a concentration 10 times greater than in
neutrons and the sulfur
Neutron Capture Therapy. (CNEA, Buenos Aires, 2010).
the rest of healthy tissue.
The vitrectomy reduces greatly the kerma in the vitreous [10] NeuSDesc: Neutron Source Description Software, EU Joint
We also include in our model the replacement of the vitreResearch Centre:
body.
ous humor by heavy water (D2O). This procedure, which can
http://publications.jrc.ec.europa.eu/repository/handle/11111be performed in practice by vitrectomy, strongly reduces the Figure 3 also shows an important decay outside the eye.
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Depth (cm)
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