Radioactivity & Radiopharmaceuticals Manik

Radioactivity and Radiopharmaceuticals
Arranged By- Md. Imran Nur Manik,B.Pharm.;M.Pharm.(Thesis) RU Page 1
Prepared BY-Shadid Uz Zaman At Tadir,.B.Pharm.;M.Pharm.(Professional) DU
Introduction:
There are some radioactive materials which are used in the field of nuclear medicine for
the diagnosis and treatment of various diseases. They are also used for imaging and functional
studies of brain, myocardium, thyroid, lungs, liver, tumors etc. In this discussion radioisotopes
(commonly referred to as radiopharmaceuticals) and their properties, effects and use shall be
discussed.
Few fundamental definitions:
Isotopes:
Atoms having the same atomic number but different mass numbers are termed isotopes
to one another.
Isotopes have the following properties-
1. Isotopes have the same number of protons.
2. But isotopes vary in the number of neutrons.
3. The isotopes have same physical and chemical properties.
4. They have different atomic mass due to variation in number of neutrons.
5. The rate of chemical reaction varies with isotopes as they have different atomic masses.
6. The natural abundance of stable forms of the isotopes of an element is always constant.
For example carbon always contains about 1% C13
6 and 99% C12
6 .
Isotopes are represented as Ay
x where x is the atomic number, y is the mass number and A is
the element.
There are two types of isotopes based on the stability.
They are –
1) Stable isotopes and
2) Unstable/radioactive isotopes.
Stable isotopes maintain their chemical integrity and do not decay to other isotopic or
elemental forms.
Exemplary, hydrogen has three isotopes H1
1 (protium), H2
1 (deuterium) and H3
1 (tritium).
Among them Protium is stable isotope and Tritium is radioactive.
Radio isotopes:
These are the isotopes of an element which are unstable therefore decompose or decay
by the emission of nuclear particles or radiations (α, β and γ radiation) to form a stable (non-
radioactive) isotope or different stable elements.
For example, among the isotopes of carbon, C14
6 is radioactive isotope.
Not all radioactive isotopes are found naturally and large number of unstable isotopes is
produced synthetically for their usefulness in many fields.
Radioactivity:
Radioactivity is the spontaneous process by which an unstable isotope of an element
decay to form stable nucleotide (stable isotope of the same element, stable isotope of different
element or elements, etc; the main point is that the new nucleus is different from the parent
nucleus) by means of emission of nuclear radiations like α-particles, β-particles and γ-radiation
etc.
Md.
Imran
Nur
Manik

Radiations of radioactive decay:
There are many types of radioactive decay particles. The major are α-particles, β-particles
including negatron and positrons, γ-rays and x-rays. They are described below.
α-particles:
These radiations are the heaviest of all radioactive emissions.
They are actually helium nucleus containing two protons and two neutrons and they are
expressed as He4
2 .
Properties:
1. It is heavy and has atomic mass equal to 4 and atomic number of 2.
2. It weighs approximately 6.6x10-24
g.
3. It is the most highly charged nuclear species with +2 charge.
4. Have very high ionizing power.
5. It has about 1/10th (0.1c) the speed of light.
6. Penetrating power is very low. It can penetrate 3-8 cm of air and can be stopped with a
sheet of paper and very thin aluminum foil. Thus they have no biological activity.
7. Usually emitted from atoms having atomic number greater than 82.
Example:
24
2
222
86
226
88

 HeRnRa
Isotopes emitting α-particles will transform into element having atomic number of two
less and mass number of four less.
β-particles:
There are actually two types of β-particles which is the β-
(negatrons) β+
(positrons)
particles. Commonly β-particles refer only to the emissions of electron (negatrons).
β⁻ particles:
β⁻ particles are emitted by unstable nuclei having unstable
proton
neutron
ratio. If the ratio is
very high/unstable, a neutron will break to form proton and electron which is radiated as β
radiation.
-
pn  1
1
1
0
It has the following properties
1. It weighs approximately 9.1x10-28
g.
2. Due to smaller weight they have greater speed than α-particles. Their speed can exceed
up to 9/10th
(0.4-0.9c) of speed of light.
3. They have greater penetrating power than α-particles. They can penetrate about 10-15cm
of water or 1-inch of aluminum as well as human tissue.
4. They have ionizing power due to presence of charge (but this is less than that of α-
particles).
5. Have useful biological applications due to penetration of tissue.
Example of β⁻ radiation is
)(14
7
14
6 particles
 -
eNC
Md.
Imran
Nur
Manik

Elements undergoing this type of transformation will form the element having the next
higher atomic number.
β+
particles:
β+
particles are emitted by nuclei having a
neutron
proton
ratio above the stable limits. In this
case, a proton is transformed into neutron accompanied by emission of a positron (which is the
antiparticle of electron having positive charge, all the remaining properties are identical).
)(1
0
1
1 particles
 enp
They are very short lived and react with electrons to produce γ rays. So they have low
penetration power and moderate ionizing power. Thus they are of little importance in biological
applications. Example of this type of radiation is given below-
)(65
29
65
30 particles
 eCuZn
As we can see, in this type of radiation, the unstable atom is converted to the element
with the next lowest atomic number.
γ-rays:
These are photons of electromagnetic radiation. It demonstrates both wave and particle
properties. It has following properties-
1. They have no mass and no charge.
2. They are high energy EM radiations with excellent penetrating power (greater than α
and β particles). They can cover hundreds to thousands metres in air before spending
their energy. Very thick lead or concrete is necessary for protection against γ-rays.
3. They are of very short wave length (10-10
-10-8
cm) and travel at the speed of light.
4. They have poor ionizing power. But there is an opportunity for secondary ionizations.
Example:




Ni*Ni
e*NiCo -
60
28
60
28
60
28
60
27
Effect in biological systems:
1. γ-rays can penetrate many kinds of materials like human tissue. It can easily damage the
tissues.
2. It can ionize atoms in chains of DNA, leading to the alteration of DNA. This may cause
tumors, cancer and genetic damage (mutation).
3. It can kill cells outright. This property can be used to treat cancer by killing cancer cells.
Electron capture (K-capture):
Electron capture is the process by which a proton-rich nucleotide absorbs an inner
atomic electron to form a neutron and simultaneously emits a neutrino.
nep 1
0
0
1
1
1 
This type of radiation is produced by a nucleotide with unstably high
neutron
proton
ratio with
insufficient energy (less than 1.02 MeV) to emit positron.
The electron capture occurs from mostly K-shell but also from L-shell. They are called
K-capture and L-capture respectively.
Md.
Imran
Nur
Manik

Due to the capture there is a deficiency of electrons in the K-shell (or L-shell) which is
made good by migration of electron from one of the outer shells. The migrating electron losses
energy in this process which is emitted as X-ray.
In case of K-capture or more elaborately electron capture the mass number remains
unchanged but proton number is decreased by 1 and neutron number is increased by 1.
Properties of X-rays:
1. The particle type is photon.
2. It has no mass and no charge.
3. It travels at the speed of light.
4. X-ray results in decrease of atomic number by 1 but mass number remains unchanged.
5. Penetrating power is very high but ionizing power is low.
Nuclear and chemical reactions:
Chemical reaction Nuclear reaction
Atoms are rearranged by the breaking and
forming of chemical bonds.
In nuclear reaction an element or elements (or
isotopes of the same element) are converted from
to another.
Only electrons are involved in the breaking
and forming of chemical bonds.
Protons, neutrons, electrons and other
elementary particles are involved in nuclear
reaction.
Chemical reactions are accompanied by
absorption and release of relatively small
amounts of energy.
Reactions are accompanied by absorption (?) or
release of tremendous amounts of energy.
Rate of reactions are influenced by
temperature, pressure, concentration and
catalysts.
Rate of reaction is normally not affected by
temperature, pressure and catalysts.
Chemical reaction may be spontaneous or
not.
Nuclear reactions are spontaneous.
A simple example of chemical reaction is An example of nuclear reaction is
rays)-X(MnMeV0.0059MneFe -
 55
25
55
26
Nuclear reactions:
Nuclear fission:
Nuclear fission is the breaking of a nucleus into two (or more) fragments accompanied by a
release of a large amount of energy.
Large nucleus tends to be unstable. This type of nucleus usually undergoes nuclear fission. In
this reaction, when the nucleus breaks, the sum of the masses of produced nuclei and the
neutrons is less than the mass of original nuclei.
The remainder of mass is released as energy. The process can occur spontaneous but it is slow.
But when the mother nucleus is hit with neutrons of sufficient energy the fission occurs
immediately.
3 4 4 2 2   2NaHSO H SO NaHSO SO H O
Md.
Imran
Nur
Manik

Example:
In the above example,
1. When a neutron reacts with a uranium nucleus, an intermediate is formed which breaks
and two or three neutrons are released.
2. Every one of these neutrons reacts with the next uranium nuclei producing two or three
more neutrons.
3. Thus the number of available neutrons and the fission goes on increasing and the fission
reaction becomes uncontrollable. In such case whole of the matter explodes resulting in a
great destruction. This principle is used in atomic bomb.
It may be noted that one reaction can go through different pathways. In the above example
three paths have been shown for the fission of uranium-235.
Nuclear fusion:
The reaction in which a few small (usually two) nuclei fuse together to form a single
heavy nucleus accompanied by a release of massive amount of energy is called nuclear fusion.
energynHeHH  1
0
4
2
3
1
2
1
In the fusion reaction the energy released is higher compared to that of fission reaction.
In the above example 17.59MeV energy is released/liberated.
Kinetics of radioactive decay:
The rate at which the atoms of a particular radioisotope disintegrate depend on the
degree of instability of their nuclei. Once a radioisotope is formed it will decay but it was proven
theoretically and experimentally that the radioactive changes are random in occurrence. So this
decay can be described in terms of probability.
Decay constant (λ) is the expression used to describe radioactive decay. The probability
of decay per unit time is called the decay constant (λ). A simple graph of decay kinetics is shown
below.
Suppose that N0 radioactive atoms are present initially and N atoms are present at time t.
If dN of those atoms decay in a time interval dt then we can write that
Md.
Imran
Nur
Manik

dt
dN
rateDecay
This decay rate is the time rate at which atoms undergo radioactive disintegration. The negative
sign indicates that the number of atom decreases with time.
Now, the rate of decay is proportional to the no. of atoms (N) present at any time (t). So we can
write-
dt
N
dN
N
dt
dN
N
dt
dN





If we integrate the last equation for a period of time between t = 0 and t = t, then
 
tN
N
dt
N
dN
00

)2...(..........
)1.....(..........
ln
)0(lnln
][][ln
][][ln
0
0
0
0
0
0
0
0
0
t
t
tN
N
tN
N
N
N
t
eNN
e
N
N
t
N
N
tNN
tN
tN
dt
N
dN
o















  
The equation (2) is a first order exponential function i.e. the decay of radioactive atoms
is a first order reaction. If the logarithm of activity is plotted against time a straight line results
with a slope of –λ.
Half life:
Half-life is the time required for the given number of radioactive atoms to diminish to
half of its original value. It is represented by 21/t .
Md.
Imran
Nur
Manik

In 21/t , 5.0
0

N
N
. So from equation (1) we can write-



693.0
2ln
5.0
2/1 



t
t1/2
t1/2
e
Both λ and 21/t are constants which characterize the rate of decay, but 21/t is more
convenient for general use.
Units of radioactivity
Radiation dosimetry:
Radiation dosimetry deals with the calculation of dose of radiation exposed to animate
and inanimate objects and the dose absorbed by them.
Exposure dose:
The exposure dose refers to the amount of radiation available for interaction with some
target material either animate (like man and animal) or inanimate.
It is the quantity of the harmful radiation in the surrounding of a particular area.
Absorbed dose:
It is the amount of radiation energy deposited on a medium (both animate and
inanimate) per unit mass of the medium.
There are few units which are required for the specification of the exposure and absorption
dose. Such units are
i. Curie
ii. Roentgen
iii. Rad etc.
Curie:
It is the fundamental unit to express radioactivity.
It is defined as the amount of a radioactive material in which 10
107.3  number of atoms
disintegrates per second. It is expressed as Ci.
BqdecayCi 1010
107.3sec/107.31 
Since Curie an excessively large unit for most purposes millicurie and microcurie are used.
sec/107.310101
sec/107.3101
436
73
decaymCiCiCi
decayCimCi





Currently it has been replaced by Becquerel (Bq) which indicates one decay per second.
Roentgen:
The exposure dose is often measured with the help of the unit Roentgen (r). It should be
remembered that roentgen unit is used for X-ray and γ-rays only and the effect must be limited
to air. It is not a unit for α- or β-radiations.
Md.
Imran
Nur
Manik

The Roentgen is defined as the quantity of X- or γ-radiation produced in 0.0001293 g of
ions carrying 1 e.s.u of charge.
The exposure dose is usually measured as a dose rate at a particular distance from the
radiation source. For example the dose can be reported as roentgen/hour/meter indicating the
number of roentgens measured per hour at 1 meter from the source.
Rad:
The basic unit employed to specify an absorbed dose is the Rad (rad = radiation
absorbed dose).
It is defined as the quantity of radiation from any source that delivers 7
10100 joules
(100 ergs) of energy per gram of tissue or other specified medium.
Exposure and effect of radiation on biological system
Sources of radiation:
i. The radioactive materials present in the earth’s crust.
ii. Cosmic rays form outer space
iii. Radon and its isotope Thoron.
iv. All foods which are naturally γ-radioactive.
Effect on the biological system: The direct effects of exposure to radiation includes
i. Inactivation of essential enzymes
ii. Coagulation of proteins
iii. Fragmentation and cross-linking of DNA, RNA and polysaccharide etc.
These effects results from an ionization or excitation of biologically active molecules.
The occurrence of an ion cluster within such a molecule releases sufficient energy to cause
abnormal chemical reactions and impair many biological functions.
Indirect effects occur due to the production free radicals by action of radiation on water
molecules present in the tissues.
In the presence of atmospheric oxygen obtained by inhalation further reaction is
possible-
The powerful activity H2O2, OH● and HO2● free radicals are thought to be responsible
for destructive effects on various tissue or organ.
Md.
Imran
Nur
Manik

They can further produce free radicals from other molecules and resulting in the
introduction of potentially toxic free radicals in the body which can alter DNA and cause cross-
linking in amino acids.
Damages in the body by radiation:
Actively dividing cells (cells in the skin & hair, reproductive cells, blood cells etc.) are
most sensitive towards radiation and following effects are observed-
Skin damage:
Short term exposure to radiation produces erythema (redness of the skin) while long
term exposure can produce brittleness and dryness of skin as well as loss of hair,burns etc.
Somatic damage:
It may cause cataract, severe anemia, leukemia, cancer etc.
Genetic change:
Radiation produces various toxic substances in the body and alters the DNA. Thus it
increases the frequency of genetic mutation.
Thus any exposure to ionizing radiations even if it is too low to cause radiation sickness
can induce the risk of cancer due to genetic mutation. It is one of the biggest risks of radiation.
Questions:
What are radiopharmaceuticals? What are the common means of measuring
radioactivity in diagnostic procedures?
α-particles are useless whereas γ-ray has widespread biological importance – why?
State and explain the biological importance of importance of radiation.
Show the kinetics of radioactive decay.
Compare the properties of radioactive decay particles.
What is K-capture? Shoe the kinetics of radioactive decay.
Md.
Imran
Nur
Manik

Radioactivity & Radiopharmaceuticals Manik

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