Vascular brachytherapy and stent restenosis

Alpha particle vascular

brachytherapy in the treatment
of in-stent restenosis

Karimi H, Mehdizadeh AR, Fazelzadeh A

Sadra–Sina Interdisciplinary Research Group
Mashad University of Medical Sciences

Abstract After percutaneous coronary

In-stent Restenosis (ISR) is the Achilles
heel for using of stent. Vascular
brachytherapy (VBT) has been the
principal scientifically investigated local
therapy for coronary artery ISR. In our
suggested method, a new type of stent,
which is coated with Boron (10B)
compound, is used. The coating layer of
the stent consists of stable isotype of
10
B. Boron Neutron Capture Therapy
produced alpha particle has enough
energy to kill the cells adjacent to the
stent, which is the site of boron
deposition. It would prevent from ISR
and intimal proliferation.
intervention (PCI) and insertion of stent,
follow-up should be done continuously,
and if ISR is detected, BNCT will be
used to treat the recurrence. Using this
modality of VBT would help us to
overcome the pitfalls in en vogue
radiotherapy methods.
Keywords: stent, restenosis, coronary
artery disease, vascular brachytherapy,
Boron neutron capture therapy, alpha
particle

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Introduction
In-stent Restenosis (ISR) is the Achilles
heel of using the stent. Vascular
brachytherapy (VBT) has been the
principal scientifically investigated local
therapy for coronary artery ISR(1).VBT
has arisen some problems:
1-After VBT, ISR will be delayed rather
than prevented (2).
2-Stent thrombosis has been the only
major adverse clinical consequence of
VBT. In the absence of VBT, stent
thrombosis typically occurs soon after
the procedure, and usually within 1
month. In the setting of VBT, stent
thrombosis may be more common, and
its temporal pattern is different, with
episodes occurring between 1 and 15
months (3).
3-Involvement of cardiac structures
remote from the lesion targeted for
radiation has been another concern.
4-Excessive prolongation of procedure
duration is another concern.
Boron Neutron Capture Therapy:
Boron Neutron Capture Therapy
(BNCT) relies on initial targeting of
cells by an appropriate chemical
compound tagged with 10B. During
irradiation of the site by thermal
neutrons, (Energy < 0.5 eV), the 10B
absorbs a low energy neutron and ejects
an energetic short-range alpha particle
and lithium ion called 10B (n, alpha) 7Li
reaction which is shown in eq.1:
10
B+N→11B*(excited atom) → 4He2+ (α)
(1.47 Mev) + 7Li (0.84 Mev) + γ (0.48
Mev) (eq.1)
Thermal neutrons are the most
important for BNCT because they
initiate the 10B (n,a) 7Li capture
reaction. However, because they have a
limited depth of penetration, epithermal
neutrons, (0.5 ev < Energy < 10 kev),
which lose energy and fall into the
thermal range as they penetrate tissues,
are now preferred for clinical therapy.
Alpha particles and lithium ions, from
the 10B (n, alpha) 7Li reaction, give rise
to closely spaced ionizing events. They
have a combined path length of
approximately 12 microns, and have
high Linear Energy Transfer (LET).
LET is one of the major determining
factors of Relative Biological Effect
(RBE) of an ionizing radiation.
Method
In our suggested method, Boron (10B)
compound coated stent is used. The
coating layer of the stent consists of
stable isotype of 10B.
After insertion of stent, follow-up
should be done continuously, when ISR
is detected, BNCT will be used for
treatment. BNCT produced alpha
particles would kill the immigrant cells
in the lumen of stent (Figure 1). It
would also prevent intimal proliferation
adjacent to stent.
Discussion
BNCT could use when ISR diagnosed
even after many years of PCI and it
does not need any interventional
procedure again. It does not prolong the
catheterization and stent insertion
procedure and it could perform as an
elective process in radiotherapy ward.
Other cardiac structures are not in the
range of alpha particles therefore it is
not a problem anymore.
Even incident thermal neutron has
negligible biological effect, BNCT
produced alpha particle has enough
energy to kill the cells adjacent to the
site of boron deposition. When the
neutron fluency has been stopped, the
boron compound would become as safe
as any other non-radioactive chemical
compounds. BNCT needs thermal or
epithermal neutron source, which is not
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 Vascular brachytherapy and stent restenosis

Figure 1. Alpha particle from BNCT process would kill immigrated cells inside of the stent wall.

available widely now, neutron fluency
may seems harmful for biological
structures lied between the source and
stent, but thermal or epithermal neutron
have lower RBE than produced alpha
particles. A basic tenet of BNCT is that
the dose of neutrons delivered to the
target volume should not exceed the
tolerance of normal tissues, and this
applies to neutron beam design as well
as to treatment planning.
VBT remains a reasonable option for
patients with ISR lesions until full data
from large randomized trials comparing
drug eluting stents with VBT are
available (4) by using new technologies
coming to the field of interventional
cardiology, it is very soon to hear the
swan song of VBT yet(5).
3- Costa MA, Sabaté M, van der
Giessen WJ, et al. Late coronary
occlusion after intracoronary
brachytherapy. Circulation 1999;
100:789–792.
4- Nikas DN, Kalef-Ezra J, Katsouras
CS, et al. Long-term clinical outcome of
patients treated with beta-brachytherapy
in routine clinical practice. Int J
Cardiol. 2007; 115(2):183-9.
5- Van Limbergen E, Trepuraneni P. Is
this the swan song of endovascular
brachytherapy? Radiother Oncol. 2007;
82(1):1–4.

References
1- Oliver LN, Buttner PG, Hobson H, et
al. A meta-analysis of randomised
controlled trials assessing drug-eluting
stents and vascular brachytherapy in the
treatment of coronary artery in-stent
restenosis. Int J Cardiol .2007,
doi:10.1016/j.ijcard.2007.03.132
2- Grise MA, Massullo V, Jani S, et al.
Five-year clinical follow-up after
intracoronary radiation results of a
randomized clinical trial.
Circulation.2002; 105:2737–2740.

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