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A new 3D printed applicator with radioactive gel for conformal
brachytherapy of superficial skin tumors
Ali Pashazadeh1, Axel Boese1, Nathan J. Castro2, Dietmar W. Hutmacher3, Michael Friebe1
Abstract— Surface brachytherapy is an effective method in
the treatment of skin cancer. Current skin brachytherapy
techniques are based on the placement of a source of gamma
or X-ray photons in a close distance from the skin to irradiate
the lesion. Due to the nature of photons, radiation dose in
these methods may affect healthy tissue as well as sensitive
structures around the target. In order to minimize unwarranted
and incidental exposure, we propose a new skin brachytherapy
applicator based upon beta particles which have penetration
ranges of a few millimeters in tissue. The proposed concept
is radioactive gel housed within a pre-designed tumor-specific
applicator matching the topology of the skin lesion. The
particles mixed with the gel showed a uniform distribution
pattern, which is an essential prerequisite in having a uniform
dose profile on the skin surface. Based on the dose calculation
data from the proposed concept, the dose delivered to the
depth of 4500 µm in skin tissue is 10% of the dose delivered
to the surface of the tumor, making it suitable is treating
thin skin tumors especially when located on top of the bone.
Through the innovative combination of radioactive gel and
tumor-specific applicator, the radiation entering the skin surface
can be personalized while minimizing the adverse effects of
undesired exposure to the surrounding healthy tissue.
I. INTRODUCTION
Basal cell carcinomas and squamous cell carcinomas are
by far the most widespread cancers in the world. According
to the American cancer society, the occurrence rate of skin
cancer is estimated to be 5.4 million per year [1]. The current
gold standard treatment for skin cancer patients is physical
removal of the lesion through the use of a surgical technique
called Mohs micrographic surgery [2]. In this technique,
the suspected site of skin tissue is excised in a layer-by-
layer fashion until the tumor is removed. Even though this
procedure yields excellent control rates, it is not applicable to
all skin cancer patients. Cosmetic issues and other potential
complications at the site of tumor excision as well as age
and health status of the patient are constraints to broaden-
ing the application of the surgical procedures. Therapeutic
methods based on ionizing radiation are efficient alternatives
to surgery which can be effective in the remediation of
superficial and deep cancerous cells. It has been shown that
*This work was partly funded by the German BMBF (grant
03IPT7100X).
1Ali Pashazadeh, Axel Boese and Michael Friebe are with the chair
of Intelligent Catheter and Image Guided Procedures, Otto von Guericke
University Magdeburg, Germany ali.pashazadeh@ovgu.de
2Nathan J. Castro is with the Joint Quantum Institute and Physical
Measurements Laboratory, National Institute of Standards and Technology,
University of Maryland, College Park, Maryland 20742, USA
3Dietmar W. Hutmacher is with the Centre in Regenerative Medicine,
Institute of Health and Biomedical Innovation, Queensland University of
Technology, Kelvin Grove, Brisbane, QLD 4059, Australia
radiation has been associated with a favorable control rate
of malignancy [3], [4].
Currently, radiation therapy of skin cancer is performed using
established methods including orthovoltage therapy, electron
beam radiation therapy, high-dose-rate (HDR) brachytherapy
and electronic brachytherapy [5].
Orthovoltage therapy is a long-standing treatment which typ-
ically uses X-ray photon produced by electrons with kinetic
energies of 100-500 keV to deliver the radiation dose from
about 50 cm distance to tumors located up to 10 mm deep
[6], [7], [8]. In electron beam radiation therapy, normally the
tumor is irradiated using 4-25 MeV electrons produced by a
linear accelerator [8], [9]. Treatment based on electron beam
is usually prescribed when the skin tumor is large and located
in a flat area, but in small and irregular regions application
of this method is challenging.
HDR brachytherapy of skin tumor is based upon the use
of Iridium-192 (Ir-192) with an after-loader mechanism
contained within an applicator [10]. Ir-192 has a half-life of
73.8 days and effective photon energy of 380 keV delivering
a radiation dose at a rate of >12 Gy/h to the skin lesion.
Electronic brachytherapy systems are portable devices based
on a small X-ray source working at an energy of 50 or
69.5 kV[11]. Low energy radiation and the simple application
of these systems are the most significant advantages of these
devices.
In radiation therapy, the primary goal is to treat the tumor
while preventing undesired exposure to healthy tissue nearby
where incidental exposure may lead to complications such
as necrosis, fibrosis, and secondary skin cancer. In the case
of a skin tumor close to critical organs such as the eye or
ear, incidental irradiation may also cause ocular damage or
hearing loss. Therefore, protecting the normal and sensitive
structures around the tumor in a radiation therapy procedure
is highly important.
In the current study, we are introducing a new brachytherapy
device which utilizes beta particles instead of gamma or X-
ray photons to treat superficial skin tumors. The sharp dose
fall-off of beta particles in tissue may lead to minimal expo-
sure to the surrounding tissue and deep sensitive structures.
The two main components of the device are a three-
dimensional (3D) printed applicator, which can be person-
alized to the patient, and a radioactive gel (a mixture of
a gel and a beta-emitting isotope). While any clinically
approved beta-emitting isotope can theoretically be used,
in this applicator we selected Yttrium-90 (Y-90) due to its
interesting physical properties. Y-90 is generated through the
beta decay of Strontium-90 (Sr-90) and subsequently decays
to the stable isotope Zirconium-90 (Zr-90). It has a half-
life of 64 hours and emits beta particles with a maximum
energy of 2.27 MeV [12]. The emitted particles can penetrate
up to 11 mm in tissue, making this radioisotope suitable for
radiation therapy of small surface lesion of a few millimeters
in thickness.
Ongoing and successful clinical applications of Y-90 include
peptide receptor radionuclide therapy of neuroendocrine
tumors, radioimmunotherapy of non-Hodgkin’s lymphoma
and trans-arterial radioembolization therapy of hepatocellular
carcinoma have further encouraged us to consider this high-
energy beta-emitter in our proposed applicator [12].
In addition to developing a tangible prototype, the dose
distribution of the applicator with Y-90 radioisotope in skin
tissue was also calculated by using the VARSKIN electron
dosimetry code.
II. METHODS AND MATERIALS
The applicator fabricated in the current study was designed
for a skin tumor of an arbitrary shape of about 20 mm in
diameter. For smaller or larger tumors, its design can be
scaled accordingly to better fit the dimension and shape of
a particular lesion.
A. Applicator fabrication
The device prototype can be fabricated individually based
on the morphology of the target skin tumor. After the tumor
is outlined on the skin surface, the resultant boundary is used
as the basis to design the shape and size of the digital model
of the cavity of the applicator. This cavity is then filled with
radioactive gel to have the source for the applicator. The
depth of the cavity used in the current design was 3 mm. The
thickness of the applicator was considered 10 mm to ensure
suitable shielding for the beta radiation of Y-90 in unwanted
directions. We used SolidWorks to design the applicator then
the computer-aided design (CAD) model was imported into
Slic3r to prepare for 3D printing. A 3D printer (Formlabs,
United States) was used to fabricate the physical model of
the applicator with methacrylate photopolymers.
B. Gel preparation
To prepare the source of beta radiation for this applicator,
we needed to mix the radioactive source with a gel. However,
as this was a proof-of-concept study to illustrate our pro-
posed applicator, the experiment was initially done using the
microspheres that were no longer radioactive. This allowed
us to work in a standard laboratory without the need to go
to a hot lab. Therefore, as a surrogate to the radioactive Y-
90, we utilized cooled microspheres of Y-90 (Sirtex Medical
Limited, Australia). The micrometer size of these particles
made it possible to visually verify the distribution of Y-90
particles in the gel using an optical microscope.
In order to prepare the gel for the applicator, gelatin powder
was mixed with water at a 1:10 ratio. 0.8 ml of water
was added to 0.2 ml of microspheres then the mixture was
added to the 5 ml of liquid gel. After the microspheres were
injected into the liquid gel, the mixture was triturated 3
times to ensure homogeneous distribution. Next, part of the
mixture was injected into the cavity of the applicator as a
representative of the radioactive gel with 1 mm in thickness.
Finally, the applicator was kept at a temperature of 14 ◦
celsius for 30 minutes allowing for the gel to solidify.
C. Verification of Y-90 distribution
Y-90 microspheres distribution was visually evaluated
using an optical microscope (SZ61, Olympus, Germany) to
assess their homogenous distribution in the gel. To this end,
the rest of the liquid gel was transferred into a 150 mm petri
dish to cover its surface. Then 16 microscopic photographs
were taken in randomly selected areas of the petri dish to
count the number of microspheres in each area.
To analyze the photographs and count the microspheres,
ImageJ was used. Each original microscopic image was im-
ported and processed to be prepared for automatic counting
by the software.
D. Dose calculation
Dose distribution from this applicator with the beta-
emitting radioactive gel was calculated using VARSKIN 6.2
code. VARSKIN is a computer code to calculate skin dose
caused during handling of, or contamination by, radioactive
sources [13]. The software allows to select one of 5 prede-
fined source geometries of point, disk, cylinder, sphere or
slab. For dose estimation, we approximated the shape of the
cavity to be a cylinder of 20 mm diameter. Then, the pattern
of dose distribution was calculated along the central axis
of the cavity and within the first 5000 µm of skin tissue at
500 µm steps. As the reference dose, dose rate at the shallow
depth of 70 µm was also calculated.
III. RESULTS
The applicator used in our study with its holding frame
is shown in Fig. 1. The cavity inside the applicator can
be designed for a patient-specific tumor further extending
its application. The two tongues seen in both sides of the
applicator are used to place it in the grooves of the holder,
which keeps the applicator in the tumor site.
Homogenous distribution of the radioactivity in the gel is
crucial to ensure uniform radiation from the applicator. As
Fig. 1. Custom-built applicator for beta radiation therapy of superficial
skin tumor
TABLE I
NUMBER OF MICROSPHERES COUN TED IN PH OTOGR APHS TA KEN BY
ANOPT ICAL MICROSCOPE FROM DIFFE RENT AR EAS O F THE GEL
Image Number Counted Microspheres
1 1000
2 1117
3 994
4 1129
5 1098
6 1161
7 1085
8 1121
9 1076
10 1169
11 1116
12 1044
13 1115
14 1019
15 1049
16 981
we used nonradioactive Y-90, therefore distribution of micro-
spheres was assessed as an indicator of uniform distribution
of the activity. Number of microspheres counted by using an
optical microscope, in different areas of the gel is given in
Table I. The average of microspheres counted was 1080 with
standard deviation of 57. This observation indicated that the
microspheres inside the gel had a uniform 2D distribution.
The pattern of dose distribution from this applicator in
the skin tissue was calculated and is given in Fig. 2. As it is
seen in the figure, the dose rate at the shallow depth of 70 µm
drops by a factor of 10 at the depth of 4500 µm. The rapid
dose fall-off which is characteristic of beta radiation makes
the significant portion of the dose to be delivered within the
very first millimeters from the surface of the skin tissue.
In Fig. 3, a possible treatment workflow based on our
proposed applicator for a skin tumor is presented. Applica-
tion of a surface brachytherapy applicator is also shown for
comparison purpose.
Fig. 2. Calculated beta dose distribution in the skin tissue depth, from the
proposed applicator using VARSKIN code
Fig. 3. The workflow of the implementation of the treatment using the
proposed surface brachytherapy applicator. Top left: skin tumor delineation
including the safety margin, Top right: fixing the applicator holder in the site
of the tumor, Bottom left: placement of the surface applicator for treatment
delivery, Bottom right: Brachytherapy of a skin tumor using a conventional
surface applicator (for comparison)
IV. DISCUSSION
Application of beta-emitting isotopes for possible radiation
therapy of very thin skin tumors has been assessed in
some studies, due to their capacity in protecting underlying
sensitive structures [14], [15], [16], [17], [18], [19]. In the
current study, a new skin brachytherapy device based on
beta radiation was designed and introduced which beside the
underlying sensitive structures can also protect the healthy
tissue around the tumor surface during the treatment proce-
dure.
The interesting feature of the applicator is that it is person-
alized. This means that the size of the applicator as well as
the shape of its cavity (containment of radioactive source)
are customizable to fit each specific tumor. Image of tumor,
which is obtained by using imaging modalities, can be used
to provide the basis for generating the digital model for the
3D printer. Manufacturing using a 3D printer provides an
opportunity for ease and quick preparation of this patient-
specific surface applicator. Therefore, using this individually-
fabricated applicator, radiation is shaped before entry the
skin, sparing healthy tissue around the tumor surface.
Microspheres showed a uniform 2D distribution pattern
inside the gel. This is an essential prerequisite in reliable
application of this applicator as a brachytherapy device.
When designing this applicator based on tumor shape and
size, safety margins around the tumor is also considered to
ensure that periphery of the tumor receives enough radiation
dose when treating with this applicator. The calculated dose
pattern of beta radiation emitted from our applicator showed
that the radiation dose beyond 3000-4000 µm from the skin
tissue drops to an insignificant level, making it a suitable
treatment for superficial skin tumors located right on top of
bone or other sensitive structures.
The amount of radioactivity, treatment time as well as the
dose needed to reach a desired therapeutic outcome depend
on the size and extension of the tumor. For a typical scenario
of a small nonmelanoma cancer with a diameter of 10 mm
located on a flat area, the prescribed dose of 20 Gy can treat
the tumor in one fraction [20]. There will be an additional
safety margin of 5 mm around the tumor to include micro-
scopic extension of the lesion. Therefore, with the proposed
applicator a cavity with a 20 mm diameter can be an option
for treating such a tumor. Considering the radioactive gel
containing 250 MBq Y-90 with 1 mm thickness, the treatment
time for a prescription depth of 2 mm will be about 70
minutes in a single fraction.
The concept of radioactive gel used in this study allows for
a high-energy beta-emitting isotopes of any half-life to be
a potential source of radiation for this applicator. Because
of the fast preparation of the radioactive gel, short half-life
beta emitters, besides the long half-life isotopes, can also be
utilized in this applicator.
Our proposed brachytherapy applicator fabricated with 3D
printing technology has also an advantage in terms of radi-
ation protection considerations. Due to the physics of inter-
action of the beta radiation with matter and its attenuation
in low atomic number materials, the material used for 3D
printing of the applicator can serve as shielding. Therefore,
during the treatment course with this brachytherapy appli-
cator, the staff is not needed to leave the treating room.
Additionally, low weight of the applicator allows to fix it
directly on the site of the skin tumor without the necessity
to use a supporting arm to hold the applicator which is the
case in some of the current skin brachytherapy methods.
It should be noted that the short range of beta particles
dictates to use a very thin layer of the radioactive hydrogel.
Our dose calculation was performed with radioactive gel of
1 mm thickness. Increasing the thickness of the radioactive
gel significantly increase the self-absorption of the radiation
inside the gel. As a result, a higher amount of radioactivity
will be needed to deliver the lethal dose to the lesion in a
time that is therapeutically reasonable.
The source of the radiation for the introduced applicator is
radioactive gel. However, as an alternative to the radioactive,
the cavity of the applicator can be filled with a radioactive
cream or synthetic resin, which has been recently used as a
treatment for skin cancer [21].
V. CONCLUSION
We illustrated a new surface brachytherapy applicator
for treating superficial skin tumors using a beta-emitting
radioisotope. Combination of beta radiation therapy and 3D
printing technology appears to well confine the radiation dose
to the thin skin tumor while protecting the surrounding sen-
sitive tissue. Next development will be adding the possibility
to the current concept to modulate the intensity of radiation
to further personalize the treatment for skin cancer patients.
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