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Therapeutic Nuclear

Medicine and CancerTreatment

BY

HAFSA BATOOL



2

THERAPEUTIC NUCLEAR MEDICINE AND

CANCER TREATMENT

BY

HAFSA BATOOL

Department of Physics

University of Sargodha

Sargodha, Pakistan

(2009-11)



3



4

APPROVAL CERTIFIC

This project entitled ³THERAPEUTIC NUCLEAR MEDICINE AND CANCER

TREATMENT´ submitted by Miss HAFSA BATOOL in Partial fulfillment of the requirement

for the degree of Master in Physics is hereby approved.

Supervisor:

External Examiner:

Chairman:

««And say. ́May Lord, have mercy on them (parents) both as they did

care for me when I was littleµ.

Miss Fatima

( Lecturer )

Department of Physics

University of Sargodha

Dr. Muhammad Nawaz Tahir Department of PhysicsUniversity of Sargodha



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The Fruit of My Work is

D ed icat ed

T o my PAREN TS

W h os e Abun d ant Aff e ctions

Patronizing Encourag e m e nt

An d Se cr e t Pray e rs

Hav e Enabl ed M e to Accomplis h t h is task

An d

T o my brot he r Az he r Ras hed for h is lov e an d sinc e r e e fforts for my futur e.



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ACKNOWLEDGEMEN T

Glory is to t h at Almig h ty Alla h w h o h as, out of a d rop of flui d , cr e at ed suc h a vari e ty of cr e atur e s, rational

an d irrational! A d or ed b e t h at Cr e ator, w h o h as e stablis hed suc h a vari e ty of forms, statur e s an d vocal soun d s

among t he m, t h oug h t he ir origin is t he sam e pur e liqui d an d g e nuin e spirit an d t h anks to t he Holy Prop he t

Mu h amma d (p e ac e b e upon h im) w h o is for e v e r a torc h of gui d anc e an d lig h t of t he knowl ed g e for mankin d

w h o h as taug h t us h ig he r i de as

I, wit h dee p e motions of b e n e vol e nc e an d gratitu de , am h ig h ly t h ankful to my wort h y sup e rvisor Miss Fatima

Aslam, L e ctur e r, D e partm e nt of p h ysics, Univ e rsity of S argo dh a, S argo dh a, un de r w h os e d ynamic sup e rvision,

illustrativ e a d vic e , k ee n int e r e st an d sympat he tic b eh avior, t he pr e s e nt stu d y was accomplis hed.

I f ee l gr e at pl e asur e in ex pr e ssing my dee p s e ns e of gratitu de to our r e sp e ct ed an d aff e ctionat e c h airman Dr .

Mu h amma d Nawaz T a h ir, D e partm e nt of p h ysics, Univ e rsity of S argo dh a, S argo dh a, for t he ir constant

inspiring l e a de rs h ip an d e ncourag e m e nt .

I off e r my sinc e r e st t h anks to my aff e ctionat e par e nts, e sp e cially my mot he r, w h o always r e m e mb e r ed m e in he r

pray e rs an d rais ed he r h an d s for m e to ac h i e v e t he h ig he st goal of lif e. Wor d s ar e ina de quat e to ex pr e ss my dee p

s e ns e of lov e an d gratitu de to my sist e r, T ALHA BA T OOL for t he ir str e nuous e fforts an d e ncouraging

attitu de..

I also lik e to t h ank to my f e llow Ms . Hina Rubab for gui d anc e an d moral support for d oing t h is proj e ct .

Th anks to all non-t e ac h ing staff of D e partm e nt of P h ysics, Univ e rsity of S argo dh a, S argo dh a .

HAF S A BA T OOL



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Table of Contents

1.1 Stable Nuclei: .................................................................................................................. 11

1.2.1 Spontaneous Fission: ...................................................................................................... 12

1.2.2 Alpha Decay:................................................................................................................... 13

1.2.3 Beta Decay: .................................................................................................................... 14

1.2.3.1 Negative Beta Decay: ..................................................................................................... 14

1.2.3.2 Positive Beta Decay: ...................................................................................................... 14

1.3 Gamma Decay: .............................................................................................................. 15

1.3.1 Gamma Rays: ................................................................................................................ 15

1.3.2 Internal Conversion: ...................................................................................................... 15

2.1 Alpha Particles Radiation Interaction: ........................................................................... 16

2.2 Beta Particles Radiation interaction: ............................................................................. 16

2.3 Gamma Radiation Interaction: ...................................................................................... 17

2.3.1 Photoelectric effect: ..................................................................................................... 17

2.3.2 Compton Effect: ............................................................................................................ 19

2.3.3 Pair Production: ............................................................................................................ 19

2.4.1 Occurrence: ................................................................................................................... 20

2.4.2 Characteristic of radionuclide in nuclear medicine: ........................................................ 20

2.4.2.1 Radionuclide for Diagnostic Nuclear Medicine:.............................................................. 20

2.4.2.2 Radionuclide for Therapeutic Nuclear Medicine: ........................................................... 20

3.1.1 Thyroid gland: ................................................................................................................ 23

3.1.2 Radio isotope of iodine: ................................................................................................. 23

3.1.3.1 Hyperthyroidism:........................................................................................................... 24

3.1.3.2 Radioiodine therapy for hyperthyroidism: ..................................................................... 24

3.1.4 Thyroid Cancer:.............................................................................................................. 24

3.1.4.1 Ana plastic thyroid cancer:............................................................................................ 25

3.1.4.2 Follicular thyroid cancer: .............................................................................................. 25

3.1.4.3 Medullary thyroid cancer:............................................................................................. 25

3.1.4.4 Papillary thyroid cancer: ............................................................................................... 25



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3.1.5 Radioiodine therapy for thyroid cancer: ........................................................................... 25

3.2.1 Lymphoma: ...................................................................................................................... 27

3.2.2 Monoclonal antibodies: .................................................................................................... 28

3.2.3 90Y-ibritumomab tiuxetan (zevalin): ................................................................................. 28

3.2.4 Adverse Effect of Radioimmunotherapy: .......................................................................... 29

3.3.1 Strontium-89: .................................................................................................................. 29

3.3.2 Adverse Effects of palliative bone treatment:.................................................................. 30

3.4.1 Liver cancer: ................................................................................................................... 30

3.4.1.1 Hepato cellular carcinoma (HCC): .................................................................................. 31

3.4.1.2 Bile duct cancer: ............................................................................................................ 31

3.4.1.3 Angiosarcomas and hemangiosarcomas: ....................................................................... 31

3.4.1.4 Secondary liver cancer:.................................................................................................. 31

3.4.2 TheraSphere: .................................................................................................................... 32

3.4.3 Adverse effects of therasphere: ........................................................................................ 33



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Nuclear Medicine is the medical specialty, in which radioactive substances are injected

into the body either to diagnose or treat the disease. Nuclear medicine relies on the process of

radioactive decay of the radionuclide. Radionuclide is either injected into the vein or swallowed

in the form of capsule, then the radionuclide decays and emits radiations so the interaction of

radiation with matter is also studied to investigate the effect of radiation on living tissues.Nuclear Medicine differs from other techniques in which radiations are applied externally to

living cells such as radiology and oncology. As due to limited penetration length and minimum

absorption range they can not be used to treat internal diseases and in these techniques highly

energetic radiations are used, so these radiations cause more damage to living cells than

benefit. As Nuclear Medicine is a targeted therapy so it effect only on targeted tumor cells and

it has minimal effect on living tissues. [1]

The history of nuclear medicine begins with the discovery of radioactivity by French

Physicist, Becquerel in 1896. During 1920s and 1930s radioactive phosphorous is administered

into the animals and it was determined that metabolic process of animals can be determined by

this method. In 1946, iodine with atomic cocktail is for thyroid cancer. It was found that

Thyroid gland took up all the radioactive iodine and it destroys the cancerous cells in gland. The

nuclear medicine work spread most in 1950s and it is still growing.

Diagnostic nuclear medicine studies the specific part or organ of the body while formal

imaging techniques such as X-rays and CT scan are focus on particular section of body. In

nuclear medicine imaging PET and gallium scan are included. Imaging nuclear medicine takes

the image of internal body parts, so it helps in locating and treating the specific part of body.

Nuclear medicine imaging and Therapeutic Nuclear medicine work in coordination with eachother. One locates the diseased spot while other treats the disease. In therapeutic nuclear

medicine specific characteristic of radionuclide are used to treat the disease. As radionuclide

travels through the body and decays near the specific body part with minimum side effects on

normal tissues.



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Chapter no.1

Basic Nuclear Medicine Physics:

Any substance which has some mass and occupies some space can be called

as matter. Matter has various properties of these our concerning are only mass and charge. As

the matter is made of small units i.e. e molecules, these small units exhibit all the properties of

matter. Like if big block of NaCl is broken into small pieces then the smallest unit that has

properties of NaCl will be its molecule. After this when it is broken down, it splits into its

constituents atoms i.e. Na, Cl. Further, inside the atom negatively charged electron moves

around the positively charged nucleus, on the whole atom is neutral. Like atom nucleus is made

of neutron and protons, having zero and positive charge respectively. As like charges repel each

other then how this possible for neutron and proton to bound firmly inside the nucleus?

Actually there is short range strong nuclear force hold the nucleons together inside the nucleus.

[12]

Binding energy is the energy which is required to remove a nucleon from the

nucleus. Typically it has value between 6MeV to 9MeV. It is found that the experimentally

determined mass of nucleus is always less than the calculated mass of nucleus. This missing

mass is known as Mass Defect. The energy equivalent of this mass is given by Einsteins mass

energy equation [3]

1.1 Stable Nuclei:

All the elements do not have stable nuclei, most of the light and mid weight

elements having atomic number up to 83 are stable nuclei (exception is for technetium z = 43

and promethium z = 61 ). While all the elements having atomic number greater than 83 are

unstable nuclei. As for stable nuclei the optimal ratio for number of protons to number of

neutrons is 1: 1.

For unstable nuclei either the number of neutrons or the number of protons increases. Line

of Stability shows the number of neutrons as function of number of number of protons as

shown in figure. 1



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Figure.1

As each atom of an element have same number of protons but the number of neutrons can be

vary in the atoms of the same element. So Isotopes are such atoms of the element which have

same number of protons but differ in number of neutrons. Like there are three isotopes of

Uranium i.e. ,

, .

Isotones and Isobars are two related entities. Isotones ate atoms of different elements which

have same number of neutron but have different number of protons. Isobars are such atoms of

different elements which have same number of nucleons.

The unstable nuclei is referred to as radioisotopes or sometimes as radionuclide. [12]

1.2 Radioactive Decay:

With the increase in number of neutrons the size of nucleus increases. It moves towards

instability. Nucleus in this unstable state can not sustain until it attain the stable state by

emitting the portion of itself or by removing energy in the form Photons or Gamma rays. This

process is known as Radioactive Decay

Unstable nuclei or radionuclide decays in varies ways depending upon the energy of nuclei.

Different ways of decay are as follows:

1.2.1 Spontaneous Fission:

In this process heavy nuclei split into two or three individual nuclear fragments

and neutrons. Fragments are usually radioactive which can carry further radioactive process.



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Much energy released during fission reaction which is used to produce Atomic Bomb or in

control manner to generate electric power in nuclear reactor. The Spontaneous Fission process

in uranium is shown in figure. (2) [3]

Figure .2 Fission of Nucleus

1.2.2 Alpha Decay:

Nuclei that decay by this method are more massive, Have too large proton to neutron

ratio. Nuclei decay by emitting a nucleus; an alpha particle. Alpha particles reduce the

Z/N ratio of unstable nuclei to make it stable. As in case of Polonium , the Z/N ratio is

0.667 while after the emission of alpha particle Polonium changes to Lead by the

reaction as follows;

The resultant have Z/N ratio of about 82/124 or 0.661. The resultant nuclei have small

ratio than parent nuclei so it is more stable than its parent nuclei. In alpha decay the atomic

number of parent nuclei and daughter nuclei is different so they have different chemical

properties.

In alpha decay of nucleus change in binding energy appears as the kinetic energy of alphaparticle; as daughter nuclei and alpha particle have equal and opposite momentum. As alpha

particles have small mass so most of the kinetic energy goes to them. Because of the large mass

as compare to beta particle i.e. more than 7000 times the mass of beta particle and its charged

nature, it has short range so it can not be used for radiation therapy as it cause more damage to

living cells. [33]



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Alpha decay process in shown in figure in (3)

Figure.3 Alpha Decay

1.2.3 Beta Decay:

In the beta particle both electron and positron (anti-electron) are included. Beta decay

occurs when the nuclei have too many neutrons or have too many protons i.e. above or below

the line of stability.

1.2.3.1 Negative Beta Decay:

When the nuclei have excess number of neutrons, it is stabilized by converting the

amount of neutron into proton. Electron and anti-neutrino are also emitted as;

Proton remains inside the nucleus while the electron is emitted out so it is as negative beta

decay. In this decay law of conservation of charge and energy is obeyed. Emission of beta

particle from carbon isotope is represented by the equation;

1.2.3.2 Positive Beta Decay:When the nuclei have too much protons then it decay by changing proton into

neutron and positron (anti-electron) and neutrino is also emitted as;



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Proton is stable inside the nucleus but to obtain stability it decays. Due to positive beta decay

atomic mass remains unchanged while its atomic number reduces by 1. This is small step

towards left of stability line. As for stability the Z/N ratio should be equal to 1. Emission of

positive beta particle from nitrogen isotope can be written as;

Positron survive for a brief time after this it encounters an electron and annihilation occur, it

changes into 2 gamma rays having energy equal to the mass destroyed.

1.3 Gamma Decay:

Here although the number of neutrons and number of proton are equal but

nucleus has enough energy greater than the ground state energy means nucleus is in excited

state. This energy is removed by isomeric transitions, which may occur by gamma rays or

internal conversion.

1.3.1 Gamma Rays:

Gamma rays are third type of radiations. Photons or gamma rays are emitted by

excited nuclei; here excess nuclear energy is emitted in the form of gamma rays.

1.3.2 Internal Conversion:

y In this process excited nucleus gives its excess energy to the

electron in the orbit which causes the removal of electron from

the orbit. For this, the excess energy of nucleus should be greater

than the binding energy of electron. Due to this removal of

electron from inner orbit creates a vacancy, to fill this vacancy

electron from outer orbits comes giving its excess energy in the

form of X-rays or - rays. [12]



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Chapter no.2

Interaction of Radiation with Matter &

Radionuclide:Now discuss how the radiations interact with matter and what happen when

they interact. The reason for studying this interaction with matter is very important from the

point as it helps to understand how these radiations interact with living tissues. Radiations with

large ionizing property badly effect living cells, radiations with different modes of interaction,

range and ionizing power is used in therapeutic and diagnostic nuclear medicine. As the

detection, characterization and effect of radiation are dependent upon the radiation interaction

with matter. Alpha and Beta are direct ionizing radiation, as upon interaction they cause

ionization of matter and excitation of atoms. In indirect radiations photons or gamma rays areincluded, as they have no charge so upon interaction first transfer energy to the charge particle

like nucleus or electron by nuclear or electromagnetic interaction. [3]

2.1 Alpha Particles Radiation Interaction:

Alpha particle radiation is the most massive and largest type of radiations. Alpha

particles are helium nuclei; as it is doubly charge so its interaction with matter is very strong.

Due to their massive nature they are deviated by both electric and magnetic field. They lose

their energy by mechanism; electronic excitation and ionization. The Specific ionization of alpha

particle is very high about thousands of ion pairs per centimeters of air. As they have short

range and low penetration depth so a sheet of paper, surface layer of dead skin (epidermis) can

easily stop them. This evident, they can not be used for Diagnostic purpose.

When inhalation or ingestion of alpha particle occurs then these alpha particles

strongly interact with living cells, all of their energy is absorbed inside the body which damage

to the cell. So due to their strong ionizing property they can not be use as therapeutic nuclear

medicine, as they cause more damage than relieve. [7]

2.2 Beta Particles Radiation interaction:

Most of the radionuclide in nuclear medicine usually emits beta particles. Beta particle

may be positively or negatively charged. Beta particles lose their energy in the same way as

alpha particle do by excitation and ionization of matter, through which they are passing. The

mass of beta particle is very small as compare to alpha particle i.e. 1/7300 of alpha particle

mass. It moves faster through the medium. It penetrates a greater distance in matter than alpha



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particle. Kinetic energy of beta particles are dissipated at large area in matter so they have low

specific ionization and linear energy transfer, but they have longer range than alpha particles.

As the beta particle travels through the matter their negative charge interacts with the

negative charge of orbital electron of matters atom. It ejects it from the orbit producing ion

pair or it causes excitation. This process continues until beta particle loses all of its energy and

capture by a nucleus.

A positron is a short lived beta particle, it loses its kinetic energy as it is quickly capture

by an electron and annihilation occurs. Two gamma rays of 0.511Mev are produced. It is used to

destroy cancer cell as it causes less damage to living cells. [4]

2.3 Gamma Radiation Interaction:

Gamma rays are photons or quanta of light; they have no charge and have

zero rest mass. The energy of single photon is written as;

Here h is a Plancks constant; c is the speed of light in vacuum. In terms of commonly used

units in nuclear physics; [34]

Photons interact with matter in different ways, depending upon the energy of gamma rays and

nature of matter. Photons interact with matter in three ways;

j Photoelectric effect

j Comptons scattering

j Pair production

2.3.1 Photoelectric effect:

In this interaction, photons transfer all of its energy to the electron in the outermost orbit.

The electron is ejected with the energy equal to the binding energy of photon. Electron starts

interaction with the surrounding matter, it rapidly lose its energy.

Photon energy transferred to matter in two steps;

j In first step, photons transfer all of its energy to electron bound in atomic orbit. For this

photon energy should be greater than the binding energy of electron. If the energy of



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First step is employed in Diagnostic nuclear medicine while second step provokes for

therapeutic nuclear medicine. [10]

2.3.2 Compton Effect:

In this gamma rays transfer only a part of its energy to the electron in outer most orbits.

Due to which electron remove as beta particle and this less energetic gamma rays deflect from

their original path. This continues to interact with outer electrons and produce secondary

ionization. Compton scattering causes a change in direction of photon. Attenuation and

Absorption are the results of Compton Effect.

j As mono energetic radiation passes through any material, then the reduction in the

intensity of radiation occurs which is known as attenuation.

j Absorption refers to taking of taking of energy from the beam by the irradiated material.

It is absorbed energy. It has important radiobiological effects. [11]

2.3.3 Pair Production:

When photons of energy more than 1.02MeV closely pass through a nucleus, photons

disappear and positron and electron are produce. This effect is known as pair production.

In this interaction, particle and anti-particle are produced.

Electron interacts with surrounding atom by producing secondary ionization.

Positron encounters an electron and they annihilated, two photons each of energy

0.511MeV are produced.

This photon then loses energy by Compton Effect and photoelectric effect. [6]

2.4 Radionuclide:

Radionuclide is an atom with unstable nucleus, which is characterized by excess

energy. This nucleus removes its energy either by creating new radiation particle with in the

nucleus or else to atomic electron (in internal conversion). Radionuclide undergoes radioactive

decay and emits gamma rays or sub atomic particles. These particles constitute ionizing

radiation. Radionuclide may occur naturally or it can artificially be produced.



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2.4.1 Occurrence:

To count the total number of radionuclide is quite uncertain, but here is brief summary

about radionuclide according to half life.

The number of radioactive nuclei which have very short half life is uncountable.

There is large number of radionuclide which has very long half life so it is experimentally

not possible to measure them.

Theoretically, there are 90 nuclides which are stable.

About 255 nuclides are not observed to decay so they can be considered stable.

Experimentally, about 650 nuclides are observed to decay which have half life longer

than 60 minutes.

Including the artificially produced radionuclide, there are 3300 nuclides are known. Out

of which more than 2400 have half life shorter than 60 minutes. [9]

2.4.2 Characteristic of radionuclide in nuclear medicine:

In nuclear medicine radionuclide is used for diagnosis, for treatment of cancer and in

research. The vital importance of radionuclide is evident. In both diagnostic as well as in

therapeutic nuclear medicines different types of radionuclide are employed. So the

selection of radionuclide for diagnosis or for therapeutic is a task, in which half life and

radiation effects of radionuclide is carefully check to minimize the radiation lose.

2.4.2.1 Radionuclide for Diagnostic Nuclear Medicine:

The characteristic of radionuclide use in Diagnostic nuclear medicine is as follows;

It should possess a short half life so it can decay during the investigative process.

Radionuclide should not be either or emitting, as they have short range.

When they wrapped inside the human tissue they can not be detect outside.

It should available in highest possible specific activity i.e. it should not have toxic

or harmful effect on human tissues.

2.4.2.2 Radionuclide for Therapeutic Nuclear Medicine:

The characteristic of radionuclide use in therapeutic nuclear medicine is as follows;

Half life should not be the case in therapeutic nuclear medicine.

Radioisotopes should emit or radiations of sufficient energy to penetrate the

required part of body.



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Radionuclide should emit gamma rays to facilitate the treatment i.e. gamma rays

facilitate in locating the targeted region.

Table of radionuclide that use in therapeutic nuclear medicine. [8]

Table.1 Physical characteristic of some therapeutic radionuclide: [5]

Nuclide Half life Emission Mean Path

Length 60.0d auger 10nm

7.2h alpha 65nm

46min alpha 80nm

6.7d Beta/gamma 0.7nm 2.58d Beta/gamma 0.7nm

8.04d Beta/gamma 0.9nm



1.43d beta 2.9nm

17h Beta/gamma 3.5nm

50d Beta/gamma 3.6nm

2.67d Beta 3.9nm



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3.1.1 Thyroid gland:

The thyroid is a small, butterfly shape gland located in front of neck and below the

larynx or voice box. Thyroid glands produce hormones which affect metabolism, brain

development, breathing, heart and nervous system function, body temperature, muscle

strength, skin dryness, weight and cholesterol level. It performs vital function in thebody which helps in regulating total function of body. Thyroid hormone production is

controlled by another hormone called thyroid stimulating hormone (TSH), which

produce by pituitary gland located in brain. Thyroid gland produces hormones which

include tri iodothyronine and thyroxin. The thyroid gland as shown in figure (6)

[20]

Figure (5) Thyroid Gland

3.1.2 Radio isotope of iodine:Iodine 131 is also known as radioiodine. It has following characteristics

It is beta emitting radionuclide.

It has characteristic half life of about 8.1 days



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It emits gamma rays with energy of 364KeV and beta particle with maximum energy of

0.61MeV.

Its range inside the tissues is about 0.8mm

I-131 decays by the following process

Due to beta decay mode, I-131 is notable for mutation and death of cancerous cells. As beta

radiations can penetrate up to several millimeters thickness. I-131 is helpful in killing cancer

cells due to high energy ionizing radiations. [16]

3.1.3.1 Hyperthyroidism:

It is an autoimmune disorder. This is characterized by over activity of thyroid

gland. This condition is also known as Graves disease. In this disease thyroid gland

makes more hormones then the bodys need. As it is autoimmune disorder means body

immune system acts against its own healthy or living cells. As immune system produces

antibodies called as thyroid stimulating immunoglobulin (TSI) that attach to thyroid cells.

These TSI minimizes the action of thyroid stimulating hormone and stimulates the

thyroid gland to secret more thyroid gland. This leads to uncontrolled secretion of

thyroid hormones, as it is the results of thyroid gland over activity. Over activity of thyroid gland imbalances body metabolism. [17]

3.1.3.2 Radioiodine therapy for hyperthyroidism:

In radioiodine therapy, I-131 is ingested in the form of capsule by mouth. Actually

thyroid gland takes iodine to make thyroid hormone. Radioiodine is absorbed in the blood

stream of gastrointestinal tract. So this iodine moves towards thyroid gland cells. I-131 starts to

destroy the cells that make up the thyroid gland. It causes no damage to other cells of body.

This process continues until thyroid gland regains its activity and body metabolism balances.

[14]

3.1.4 Thyroid Cancer:

Thyroid cancer is a tumor growth in the thyroid gland. Usually the old thyroid cells

are replaced by new thyroid cells in a regular way. In some cases the replacement of old cells by



25

new cells do not follow the regular pattern and the cells begin to reproduce in uncontrolled

manner. This uncontrolled growth causes cancer. [18]

Thyroid cancer occur in the following forms

3.1.4.1 Ana plastic thyroid cancer:

It is the most severe form thyroid cancer. It is very to treat it. Fortunately only less

than 5% patients have this type of thyroid cancer.

3.1.4.2 Follicular thyroid cancer:

It occurs in 10% or 15% of all thyroid cancers. It occurs in patients of older age. It

usually grows in lymph nodes in the neck, it grows in blood vessels from here it moves towards

other parts of the body such as lungs and bones. [15]

3.1.4.3 Medullary thyroid cancer:

Medullary thyroid cancer is 5% to 10% of all types of thyroid cancers. Its cause is

genetic mutation. It usually runs in families.

3.1.4.4 Papillary thyroid cancer:

It is the most common type of thyroid cancer. It accounts 70% to 80% of all types

of thyroid cancer. It occurs more common in women than men. It spreads slowly. Mostly it

occurs in young peoples.

It is not possible to say exactly, what is the cause of thyroid cancer. Large exposure of

radiation in chest and neck area may be its cause. It can also be occur due to genetic

mutations. Due to which cells lose their control on reproduction and cells begin to

multiply in uncontrolled manner and cause cancer. [19]

3.1.5 Radioiodine therapy for thyroid cancer:

This treatment is only suitable for following type of thyroid cancer.

j Follicular thyroid cancer

j Papillary thyroid cancer

Radioiodine therapy is given in the following conditions.

j After surgery to kill any left behind cancer



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j To treat thyroid cancer that has spread

j To treat thyroid cancer, after it was first treated.

Thyroid cells obtain iodine from the blood stream to produce thyroid hormone. Thyroid

cancer cells can take only a small amount of iodine from blood stream. High level of

thyroid stimulating hormone (TSH) stimulates the thyroid cancer cell, to takes up a large

amount of iodine. When the radioactive nuclei enter the thyroid cells it starts to kill the

cancer cells. Some times to increase the uptake of Iodine the TSH level is increased by

hypothyroidism. This effect of Hypothyroidism is temporary.

The main advantage of radioiodine therapy is this is safe to use and it is possible to cure

the disease that spreads to other parts of body.

Radioiodine Therapy has less or no side effects as only sore throat is observed [13]

3.2 Radio-immunotherapy:It is the nuclear medicine cancer therapy which involves the combination of

monoclonal antibodies with radioisotopes; a source of radiations.

FIGURE.6



27

Figure .6 shows radio immunotherapy on B-lymphocytes

Radionuclide is utilized for the treatment of non- Hodgkins lymphoma by radio-

immunotherapy. As the body immunity system detects the presence of any foreign agent like

bacteria or pathogen. One way to eliminate it from the body is by producing antibodies. As the

antibodies bind to protein shape that are specific for foreign invaders. In RIT antibodies are

man made, to which different radio nuclides are attached. Antibodies are designed to attach on

the protein shape surface, called as CD20. CD20 sticks to mature B-lymphocytes. It is not found

on immature B-lymphocytes. As proliferating tumor cells are inherently sensitive to radiation.

RIT is a targeted radiation therapy that delivers radiation to specific to one type of cell.

Antibodies specially attached on the tumor associated antigen. [30]

Antibodies increases dose delivery to tumor cells while decrease dose is delivered to

normal cells. RIT delivers total body radiation in more directed fashion with focus on tumor

cells. Peak dose is generally low but radiations are delivered continuously at an exponentiallydeclining rate. This continues delivery prevents the DNA repairing. The total body clearance rate

of radioisotope depends upon the size of tumor. The injected dose is the therapeutic amount of

radioactivity administered to patient and this radioactivity is measured in mCi. The absorbed

dose is the radiation delivered to cancer cells and is measured in cGy. This process of relating

the administered dose of radioactivity to the absorbed dose of radiation to tissue is known as

Dosimetry. [29]

RIT is given in following therapeutic steps

Initial antibody dose (called as cold dose) clears the normal B-cells so subsequentdoses will focus on cancerous cells

The second dose (warm dose) has anti-tumor influences, this step involve the

clearance of body with the help of imaging techniques

The third dose (hot dose) is specially organized to kill the tumor cells [31]

3.2.1 Lymphoma:

Lymphoma is a cancer of lymph tissues. It includes the lymph nodes, spleen and

other organ of immune system or lymphatic system. Lymphatic system is a part of immune

system that defends us from bacteria, viruses and unwanted poisonous substances. White blood

cells are called as lymphocytes. These lymphocytes prevent us from infections. Lymphocytes

consist of two types of cells

j B- lymphocytes

j T-lymphocytes



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B-lymphocytes develop into plasma cells that generate antibodies to fight with

infectious agent.

T-lymphocytes invade the foreign agent directly

Lymphomas are diverse group of blood cancer that try to form solid lymph any where in the

body and felt as painless lymph.

Lymphomas have two types on the basis of how they spread, behave and respond to treatment.

Types of lymphomas are as follows

Hodgkins lymphoma

Non-Hodgkins lymphoma

Non-Hodgkins lymphoma is cured by using nuclear medicine as monoclonal antibodies.

In most cases, the cause of cancer is unknown. However it develops in those people who

have weakened immunity system e.g. Organ transplanted patient or HIV patient. [32]

3.2.2 Monoclonal antibodies:

Antibodies are normal component of body immune system. They can recognize

and destroy foreign invaders such as bacteria and viruses. Monoclonal antibodies are the

antibodies that can be produced in laboratory from a single clone, to locate and bind to specific

substance or tumor cells in the body. Scientists now produce monoclonal antibodies to

recognize specific targets or antigen that are present on cancer cell. [22]

3.2.3 90Y-ibritumomab tiuxetan (zevalin):

Ibritumomab tiuxetan is also known as Zevalin. It belongs to group of cancer drugs

known as monoclonal antibodies. It links with radioactive isotope called 90-Y. It is used for the

treatment of non-Hodgkins lymphoma. Ibritumomab is a monoclonal antibody which is

conjugated with chelates of 90-Y isotope. Yttrium is a source of beta radiations. Yttrium is a beta

emitter with half life of 64 hours. It has long path length in soft tissues of about 5.34nm.

fig.7



29

Figure (7) Antibody targeting on cell

Monoclonal antibody therapy is efficient way of specifying the required kind of cancer cells.

Zevalin is administered into the body by intravenous infusion. In the blood stream, monoclonal

antibodies travel throughout the body and attach themselves to cells which have specific target

antigen like cancer cells. This activity alters the body immune system to recognize and destroy

the bounded cells. Normal cells can be destroyed by this method but they can be cured by

further treatment. [28]

3.2.4 Adverse Effect of Radioimmunotherapy:

y temporary lowering of the blood counts , which may cause anemia

y fatigue

y nausea

3.3 Palliative Radiation Therapy:

Palliative Radiation therapy is not use to treat the disease but it is utilized to relive

from pain and suffering as result of cancer and other painful diseases. The goal to Palliative

treatment is to improve the quality of life of patient.

Bone metastasis is a class of cancer metastasis that results from primary invasion to bone. The

bone metastasis causes severe pain, which grows worse with time. Palliative radiation

treatment can be used to give relieve to the patient of bone metastasis but this treatment can

not be used to cure the disease. [23]

3.3.1 Strontium-89:

As the bone metastasis is malignant cancer which spreads to skeleton from breast or

prostate cancer. Strontium-89 is a radionuclide which is used for the cancer treatment from

nearly 50 years. But its importance is increase in now-a-days due to increasing number of

people suffering from this disease. Other radioisotopes like P-32, I-131, Y-90 are also use for thispurpose. But Sr-89 is the most efficient radioisotope for this purpose. There is a physiological

analogy between Sr-89 and Ca-40. Osteocytes are the basic unit of bone. Osteoblasts tissues

form the bone tissues while osteoclasts refresh the bone tissues by secreting enzymes which

destroy the old tissues.



30

Strontium-89 is a pure beta emitter which has a short half life of 50.5 days in tumor cells

while in normal cells it has half life of about 14 days. It decays by the following processes

It is a beta emitter with energy 1.463Mev. Sr-89 has maximum range of about 8mm in livingcells. Absorb dose will be 200MBq. Sr-89 can either be produced in cyclotron or by irradiation of

Sr-88 with gamma rays in nuclear reactor. [21]

Palliative bone pain radiation therapy provides 25% to 80% relieve to patient. It is not for

to cure disease but it is used to reduce pain. High dose of radionuclide is required as compare to

diagnostic scan. Radionuclide inserted into the body by intravenous catheter. A catheter is a

small capillary tube that is put into the vein. Radioactive material will gather at the active site

and irradiates the bone area. Sr-89 emits beta radiations. Absorb dose is calculated in both the

metastasis tumor cells and normal cells. It is found that uptake of Sr-89 in bone is so high that

the amount of Sr-89 decreases per absorb dose. The ratio of absorb dose in bone metastasis

and in normal cells is about 10:1. By acting on peripheral nerve cells, it exerts a cytotoxic effect

on metastasis tumor cells, where inflammatory cells, tumor cells and cells with inmmunitary

activity and chemical substance modify the pain causing agents. [37]

3.3.2 Adverse Effects of palliative bone treatment:

y Fatigue

y loss of appetite

y damage to the surrounding cells

3.4 Radioembolization therapy:

In radioembolization therapy body anatomy system is utilized to deliver large dose of

radiation to tumor cells and it has minimal effects to normal cells. In this therapy radioactive

substance of the very tiny size is employed. Liver cancer can be cured by this therapy.

3.4.1 L

iver cancer:Hepato cellular carcinoma or liver cancer is the sixth common form of cancer and is

the third most common cause of deaths due to cancer. Mostly it is diagnosed in the

advanced stage of disease. To understand the liver caner it is importance first to

understand the function of liver. Liver is largest vital organ in the body. It is located under



31

the right rib just below the right lung. It has pyramidal shape and for convenience it is

categorized as left and right lobes. Liver obtains blood from two sources

Hepatic artery supplies the liver with oxygenated blood

Portal artery carries the nutrient rich blood from intestine to liver

Liver cancer can be classified as

3.4.1.1 Hepato cellular carcinoma (HCC):

It is most common type of cancer that usually found in adults. It is start in liver

cells. HCC have different growth pattern which are as follows

Some times it starts in single and spreads to other parts of body may be start in the form

of spots in liver but not as a single cell

In some cases it starts in the form of spots on liver and it is not start from single cell. Itspreads randomly

3.4.1.2 Bile duct cancer:

It occurs in small tubes that carry bile to gall bladder. Out of total 10 liver cancer

cases 1 or 2 are this type of cancer.

3.4.1.3 Angiosarcomas and hemangiosarcomas:

These Cancers occur in the blood vessels in the liver. It is the rare type of cancer. Itspreads quickly and also to other organs. It is difficult to cure.

3.4.1.4 Secondary liver cancer:

Cancer begins to grow in liver due to cancer in other organs. This type of cancer

is known as metastatic cancer. Although these are in liver but they look the cells of the organ

from where they come. [35]



32

Figure 8 Liver Cancer

3.4.2 TheraSphere:

Non radiation therapy like surgical treatment cause more damage to normal

cells. In case of external beam radiations, the required dose to kill tumor cells is greater than

70Gy while liver parenchyma tissues have tolerance for only 35Gy. External radiation therapy

despite to kill tumor cells kill the normal cells, moreover it disrupts the DNA. [25] With the

development in internal radiation the hazard is reduced as it is a targeted therapy.

Radioembolization therapy is a targeted and directed therapy to kill tumor cells while living

normal cells. Radioembolization by using therasphere is a new concept for the treatment of

liver cancer. [27]

TheraSphere is a new form of cancer treatment that directly targets the tumors in the liver

using small glass beads. These glass beads contain 90-Y as the integral part of its constituent. 90-

Y is a radioisotope which is a source of beta-radiation emitter which kills the tumor cells. Y-90

has physical half life of 2.67 days or 64.2 hours. The average range to irradiated tissues is about



33

2.5mm. Its maximum penetration is about 1.0cm. Each microsphere have diameter of about

25µ-35µ. 1GBq or 27mCi of Y-90 delivers a total absorbed radiation dose of 50Gy/kg. In

therapeutic nuclear medicine, isotope decays to infinity and 94% of radiation delivered in 11

days. [26]

Normal liver cells receive 85% of blood supply from portal vein and 15% of blood via hepatic

artery. Tumor cells parasitize the blood from hepatic artery, so these cells receive 80%-100% of

their blood from hepatic artery. So this dependence on hepatic artery is exploited in order to

reduce loss for normal cells. A catheter is inserted in to femoral artery of leg, which is joined

further to form the hepatic artery. Through catheter small but large number of microsphere

entered into small blood vessels that supply to tumor cells. They block the flow of blood. Here

these spheres emit radiations and kill the cancer cells.

Figure (9) Blood Flow and Microsphere Distribution in Liver Tumor

3.4.3 Adverse effects of therasphere:

y Stomach pain

y Nausea

y Vomiting

y Fever

y Fatigue[24]



34

Conclusion:

With the immense spread in cancer and other horrified diseases, death rate was

increased at a very high rate in last era. Moreover, the treatment which is provided to treatthese threatening diseases was again very painful. As highly energetic radiations was used to

treat cancer, which destroys not only cancer cells but kills normal cells as well and other side

effects are also reported. With the development in nuclear medicine not only the survival rate

increase but also side effects on normal cells are also reduced by using targeted cell therapy and

also the quality of living of patient is improve.



35

References:

[1] Paper of Nuclear Medicine by Ramsey D Badawi

[2] Techniques for Delivery of Radiation therapy by Dr. Reshma L. Mahtani

[3] Basic Physics of Nuclear Medicine by Kieran Maher

[4] Beta radiation interaction, gamma radiation interaction by Patrick Muldoon

[5] Ch_13 therapeutic radionuclide.pdf

[6] Radiation interaction with matter from European center technological safety

[7] Interaction of radiation with matter by university of Toronto of environmental health

and safety

[8] Radioisotopes in Nuclear Medicine from world nuclear association by Rex Boyd

[9] Carlsson J et al. : Tumor therapy with radionuclides: assessment of progress and

problems

[10] Interaction of radiation with matter by Perry Sprawls

[11] Interaction of radiation with matter by Dr. Santam Chakraborty

[12] Essential nuclear medicine physics by Rachel A Powsne, Edward R. Powsner

[13] Nuclear Medicine in Thyroid Cancer management by IAEA

[14] Radioiodine therapy from AACE Radioiodine_Therapy.pdf by American Association of

Clinical endrocrinologists

[15] Cancer of Thyroid by American Thyroid Association

[16] Radioactive Iodine-131 from Fallout

[17] Therapeutic application of radiopharmaceutical by IAEA

[18] Thyroid Cancer by Leonard wartofsky and Douglas Van Nostrand

[19] Thyroid cancer by David C. Dugdale and David Zieve



36

[20] Graves disease from by National institute of diabetes and digestive and kidney diseases

[21] Research paper on: Quality control method of strontium chloride, pharmaceutical for

palliative treatment of bone metastasis by CZ DEPTULA, T KEMPISTY, A MARKIEWICZ, RMKOLAHCZAK, STEFANCZYK, T TERLDCOWSKA, W ZULCZYK

[22] Monoclonal Antibody therapy for B-cell non-Hodgkins lymphoma by Bruce D. Cheson,

John P. Leonard

[23] Palliative Radiation and cancer care by Gil Lederman

[24] TheraSphere by Mark Jordan

[25] Y-90 Radioembolization for the treatment of Metastic liver cancer by Micheal Cohn

[26] Yattrium-90 Radioembolization by Dr. Douglas Coldwell

[27] Research paper: Radioembolization with Y-90 microspheres for the treatment of

heptocellular carcinoma and liver metastasis by Raid Salem, Laura Kulik, Ravi Murthy

[28] Zevalin by Leo.I. Gordon

[29] Y-90 Ibritumumab tiuxetan (zevalin) by P.I zinzani

[30] Radioimmunotherapy by lymphoma organization

[31] Therapeutic immuno-conjugates in the treatment of hematologic malignances by Paul

A. Hamilin

[32] Non-Hodgkis Lymphoma by David c. Dugdale

[33] The ABC of nuclear science by Howard Matis

[34] Radioactivity by Car. R (Rod) Nave of Georgia state university

[35] Interaction of radiation with matter by Dr. Manjula Sharma

[36] Liver cancer by American cancer society

[37] Metastatic bone pain management with radioactive isotope by Juan Coya Vina

therapeutic nuclear medicine and cancer treatment

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