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Procedia Materials Science 10 (2015) 603 – 608

2nd International Conference on Nanomaterials and Technologies (CNT 2014)

Scope of Nanotechnology in Radiation Treatment Planning

S P KISHORE a,N V S L Narasimham b,A Ramakrishna Prasad c
Vardhaman College of Engineering, Department of Freshman Engineering, Shamshabad, Hyderabad-501218, INDIA
b
GNITS, Department of Mathematics, Shaikpet,Hyderabad-500008,INDIA
c
JNTUH ,Department of Mathematics, Hyderabad -500085 ,INDIA

Abstract

In this paper an attempt has been made to study some of the elements of mathematical modeling in solid tumor growth. We
present simple deterministic mathematical models used to describe tumor growth. Radiation therapy can be made very effective
through the use of nanoscale particles such as gold nanoparticles, carbon nanotubes and magnetic nanoparticles. Development of
a model using all the necessary biological assumption has been illustrated through an example. A large number of drug delivery
systems have been developed over the years to overcome the challenges in cancer treatment and hence improve the right balance
between effectiveness and toxicity. Finally we present various aspects of our methods and their results .The results demonstrate
that the use of nanoscale particles in radiation treatment planning holds a lot of potential to improve the efficiency of the
treatment.

©
© 2015
2015The TheAuthors. Published
Authors. by Elsevier
Published Ltd. This
by Elsevier Ltd. is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peer-review under responsibility of the International Conference on Nanomaterials and Technologies (CNT 2014).
Peer-review under responsibility of the International Conference on Nanomaterials and Technologies (CNT 2014)
Keywords: mathematical modelling; nanotechnology; radiation therapy, gold nanoparticles (GNPs) ;carbon nanotubes (CNT).

1. Introduction

A Mathematical model is an abstract mathematical expression used to describe the behaviour of the system. A
tumor growth model gives the measure of tumour volume at a specified period of time. In this section we discuss
some of the deterministic and probabilistic mathematical models currently in use to understand the growth of tumor.
Mathematical modelling problems are classified as white box or black box models. Mathematical modelling in
general consists of three stages:
x defining the problem
x testing the model
x acceptance or rejection of model

2211-8128 © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peer-review under responsibility of the International Conference on Nanomaterials and Technologies (CNT 2014)
doi:10.1016/j.mspro.2015.06.012
604 S.P. Kishore et al. / Procedia Materials Science 10 (2015) 603 – 608

In the first stage, model is defined considering all the necessary biological assumptions. In the second stage the
model is tested against the experimental data by selecting a suitable test statistic. The model evaluation part is one of
the crucial parts in modelling as it shows whether the data suffice to explain the model accurately or not. In the
third stage we draw all the inferences and conclude by accepting or rejecting a model. If a model is rejected then
necessary changes are made in assumptions. Sometimes a model is rejected if there is inadequate number of
assumptions or wrong assumption(s).
Radiation treatment planning to a cancer patient has been improving all the time and it shows a lot of promise in
near future. Tumors are treated primarily using one or combination of the following methods: chemotherapy,
surgery, radiotherapy (internal and external beam radiotherapy).There are some more methods used to treat
cancerous tumors like thermotherapy, biological therapy, hormone therapy and stem cell therapy.

In the current scenario of radiation treatment nano particles have a huge role to play because of its unexpected
optical, mechanical and magnetic properties. Nowadays nanotechnology is used in almost all the areas of health care
and particularly so in radiotherapy. The medical application of nanotechnology is also referred as nanomedicine.
Cancer Nanotechnology provides a larger picture of the methods currently used in cancer therapy and to an extent
provides promising solutions to many of the therapies. Radiotherapy can be made effective through the use of
nanoscale particles. The major aim in developing a nanoscale particle in drug delivery system is to enhance the
therapeutic effect and in turn reduce the toxicity of other active materials. Gold nanoparticles have the potential to
be useful in therapeutic situations as they come with a size of 50 nm. Carbon nanotubes are generally used in
photodynamic irradiation therapy of targeted cancerous cells.In photodynamic irradiation therapy,carbon nanotubes
are targeted to tumor tissues using a small molecular compound or a specific tumor antibody and are irradiated with
an near infra-red lasers(NIR).carbon nanotubes are synthesized mainly by the methods, laser ablation,arc discharge
synthesis and chemical vapour deposition. The size of carbon nanotubes is less than 100 nm. Magnetic nanoparticles
have a size of 10 nm and are synthesized by co-precipitation of Fe 2 + and Fe 3+ aqueous salts and by adding a
suitable base.

2. Some Mathematical Models

The mathematical models are generally divided into three categories: Empirical models, Functional models and
structural models. In this paper a study has been made of empirical models with respect to their metabolic
considerations.

Simple Exponential growth curve is given by

dL
OL ;O ! 0
dt (1)

where L denotes the total number of carcinogenic cells and O denotes the intrinsic growth rate. Equation (1) has a
solution
L(t ) L(t0 )eO (t t0 ) (2)
where L(t0 ) is the tumor size at time t t0 .
Since the growth is unrestricted verhulst et al.considered that for a stable growth a saturation level has to be
KN
achieved. To achieve this tumor growth model a multiplier is used which represents the fraction of the
K
current size from the saturation level K .The well known logistic growth equation can be obtained by expanding
f ( L) by Taylor series method at origin. The Taylor series in one variable is given by
 S.P. Kishore et al. / Procedia Materials Science 10 (2015) 603 – 608 605

L2 L2
f ( L) f (0)  Lf c(0)  f cc(0)  f ccc(0)  ......
2! 3! (3)
Neglecting the higher order terms, we get
L2
f ( L) f (0)  Lf c(0)  f cc(0)
2! (4)
Since, initially a zero population has a zero growth, we have f (0) 0
Therefore, we obtain
ª L º
f ( L) L « f c(0)  f cc(0) »
¬ 2 ¼ (5)
2O
By setting f c(0) O and f cc(0) ,one obtains the Logistic growth equation
k
dL ª Lº
O L «1 
dt ¬ K »¼ (6)

where O and K are constants.

This logistic differential equation gives the recovery time of the non cancerous cells after they have been distributed
by the same internal and external forces. If initially at t t0 ,we have L(t0 ) L0 ,then L0 ! K or L0  K ,where
K is the carrying capacity. The tumor growth level for the time t ! t0 is given by the solution of the logistic
differential equation (6)
1
L(t )
1 § 1 1 ·  O (t t0 )
¨  ¸e
K © L0 K ¹
(7)
shows the graph of the solution of the logistic equation when L0 is greater than, is equal to or is less than the
saturation level. The expression (7) is assumed to hold good after a single irradiation of normal cells. In the
procedure of radiation treatment planning the restitution of normal cells is incomplete and this will affect the
carrying capacity K .
The growth pattern in all the tumors is more or less the same. All the tumors increase rapidly in the beginning, till
they reach the maximum size. The main disadvantage in simple exponential growth model is that it is unable to
model the behavior in vivo.

The generalized Logistic equation is given by

Q
dL ª § L ·E º
O L «1  ¨ ¸ »
D

dt «¬ © K ¹ »¼ (8)
Equation (8) includes as a special case the well known logistic differential equation (D 1, E 1,Q 1) ,
Blumberg’s growth equation ( E 1) and the Richard equation (D 1,Q 1) .All the three models have been used
to describe the tumor growth. It is very interesting to note that the generalized logistic growth equation gives arise to
two important models of tumor growth based on their metabolic considerations .ForQ 1 , the generalized logistic
2 1
growth equation reduces to Von Bertalanffy equation (D ,E ) , given by
3 3
606 S.P. Kishore et al. / Procedia Materials Science 10 (2015) 603 – 608

2ª 1
º
dL § ·3
L
O L «1  ¨ ¸ »
3
dt « ©K¹ »
¬ ¼ (9)
Solution of the differential equation (4) gives
3
­ ¨  Ot ¸ ½
§ ·

°° ª § L · 3 º ¨¨ 13 ¸¸ °°
1

L(t ) K ®1  «1  ¨ 0 ¸ » e© 3 K ¹ ¾
° «¬ © K ¹ »¼ °
°¯ °¿ (10)

According to Von Bertalanffy et al. the rate of degradation and the rate of growth are proportional to the power of
the tumor volume. Based on the metabolic considerations we have considered two more growth models, The first
growth model is given by
3ª 1
º
dL § L · 4
O L «1  ¨ ¸ »
4
dt « ©K¹ »
¬ ¼ (11)
and the solution of the differential equation (11) is obtained by setting L L0 at t 0 , and it can be written as
4
­ ¨  Ot ¸ ½
§ ·

°° ª 1
º
§ L0 · 4 » ¨© 4 K 4 ¸¹ °°
¨ 1 ¸

L(t ) «
K ®1  1  ¨ ¸ e ¾
° «¬ © K ¹ »¼ °
¯° ¿° (12)
The second growth model is given by
ª
1
3
º
dL § L · 4
OL 1 ¨ ¸ »
«
4
dt « ©K¹ »
¬ ¼ (13)
and the solution of the differential equation (13) is obtained by setting L L0 at t 0 , and can be written as
4
­ ¨  Ot ¸ ½
§ ·

°° ª § L · 4 º ¨¨ 34 ¸¸ °°
3

L(t ) K ®1  «1  ¨ 0 ¸ » e© 4 K ¹ ¾
° «¬ © K ¹ »¼ °
¯° ¿° (14)

Gompertz growth curve can be derived as a special case of the generalized two parameter model of growth. It is
described by the equation

dL ª Kº
O L «ln
dt ¬ L »¼ (15)

George W Swan et al. reduced the non linear differential equation (7) to a linear one by the transformation
 S.P. Kishore et al. / Procedia Materials Science 10 (2015) 603 – 608 607

K
X ln
L (16)
and the solution of the differential equation (16) can be written in the form of
§K·
 ln ¨ ¸e O ( t t0 )
© L0 ¹
L Ke (17)

3. Gold Nanoparicles (GNPs)

Nanoscale particles exhibit a lot of unusual optical, electronic and magnetic properties .Interestingly GNPs have
attracted a lot of attention in health care system because of its physicochemical properties.GNPs efficiency has
already been demonstrated in vitro and in vivo in a mathematical model on mice.GNPs have been synthesized from
the 19th century, they can enter into the cells and act as novel agents in cancer therapy. The two common methods
for the production of GNPs are
x Produced in a liquid by citrate reduction of Au3+ such as aurochloric acid (Haucl4) in water to Au0+

x Two phase synthesis and stabilization by thiols.

4. Carbon Nanotubes(CNTs)

Carbon nanotubes are synthesized mainly by the methods, laser ablation, arc discharge synthesis, plasma torch,
removal of catalysts and chemical vapour deposition. CNTs can be categorized by their structure as single- wall,
double-wall and Multi-wall Nanotubes. Additionally, there are some of the the carbon nanotubes which are
biodegradable such as polyhydroxyalkanoates.The strength and flexibility of CNTs make them of potential use and
has garnered a lot of attention in real time research because of its mechanical, electrical,physical and chemical
properties. As more and more CNTs will be produced in near future, the main goal would be to understand the
toxicity of it. To obtain more accurate results researchers should use more reliable methods for detection. However,
long term application of carbon nanotubes may be associated with cancer risk. Table 1 briefly depicts the
Applications and toxicity of GNPs and CNTs.

Applications Toxicity
x Photo thermal therapy S kin reactions
x Specific target tissues or cells in radiotherapy
x Used as radiosensitisers
Gold Nanoparticles x Excellent drug delivery vehicles
x Cancer imaging
x Anti-cancer conjugates

x Micro beam radiotherapy x Oxidation stress

x Used in biomedical applications x Inflammatory responses
x In vivo and in vitro analysis, they move into cells x Malignant transformation
Carbon Nanotubes by receptor mediated endocytosis x Interstitial fibrosis
x X-ray source array surrounding the target of x DNA damage and mutation
irradiation
x Low cost MRT devices
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5. Conclusions

It is significant to mention that the models used here to describe tumor growth are capable enough to be
evaluated. Some other basis, such as estimation of parameters, biological considerations and prediction of the
growth of the curve by calculating the tumor doubling time can be used for selecting an appropriate model.
Since GNPs have a high atomic number, so they have more capacity of absorption of kilo voltage X- rays, which
helps us to use them as contrast agents. GNPs come in lot of sizes varying from 1 nm to 50 nm, so they can easily
penetrate throughout the body and can easily accumulated at the tumor site At kilo voltage photon energy,
nanoparticles of gold can cause radiosensitisation.Lot of research is been carried in checking the toxicity of GNPs,
so it has got the potential to be used in clinical trials. On a global scale, lot of efforts in nanotechnology has been
seen, so a lot of scope there and the questions pertaining to GNPs will be addressed in a rigorous way in future by
keeping a check on its toxicity.CNTs are extremely versatile as they can be used in many fields owing to their
excellent material properties. Therefore more study on toxicity of GNPs and CNTs are recommended so that they
can augment the available data. Nanotechnology in radiotherapy is a relatively unexplored area and the rate at which
the research is been carried out is highly commendable, so in near future a lot of nano materials will be used in
cancer treatment.

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