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RADIOCHEMICAL

TECHNIQUES

PHARMACEUTICAL RADIOCHEMISTRY
AND NUCLEAR PHARMACY
PHARMACEUTICAL RADIOCHEMISTRY

It is the branch of chemistry that deals with the


radioactive substances, that are used for diagnosis and
therapeutic uses.
It deals with the study of radioactive isotopes,
radioactive decay, radioactive half-life and
measurement of radioactivity of radioactive isotopes.
NUCLEAR PHARMACY

It is the specialty area of pharmacy practice dedicated


to the compounding and dispensing of radioactive
materials for use in nuclear medicine procedures.
It also deals with the employment of radioactive
substances for diagnostic, therapeutic and analytical
purposes.
Introduction to Radiochemical Techniques

Method of Radiation

Radioactive Isotopes
INTRODUCTION TO RADIOCHEMICAL TECHNIQUES

These techniques are used to monitor radiation from unstable


atomic nuclei
The intensity of the emitted particles or electromagnetic radiation
is used for quantitative analysis
Energy of the emissions is used for qualitative analysis
INTRODUCTION TO RADIOCHEMICAL TECHNIQUES

Radiochemical
method
depend upon

Type of Energy of
Half Life of
emitted emitted
particles
radiation radiation
HALF LIFE

It is abbreviated as t1/2
It is the time taken for the radioactivity of a specified
isotope to fall to half its initial value
Iodine-131 has half life of 8.1days
METHODS OF RADIATION

Method of
radiation

Activation
analysis/Neutron
Tracer method Isotope dilution
activation analysis
(NAA)
NEUTRON ACTIVATION ANALYSIS

Few analyte are naturally radioactive


For many analyte, we can induce radioactivity by irradiating the
sample with neutrons by this process
It is an extremely sensitive technique of radiochemical analysis
used to determine the existence and quantities of major, minor
and trace elements in a material sample
NEUTRON ACTIVATION ANALYSIS
NEUTRON ACTIVATION ANALYSIS

As opposed to other methods in analytical chemistry, it focuses


entirely on the nuclei of atoms and not their molecular structure
When sample are irradiated with neutrons, certain of their
elements become radioactive and emit gamma rays of various
energies
This emitted radiation is a fingerprint of the element, and the
amount of radiation given off at a certain energy is indicative of the
amount of the element present in the sample
NEUTRON ACTIVATION ANALYSIS

A comparison between specific activities induced in the standards


and unknowns provides the basis for computation of elemental
abundances.
From this analysis-a report is issued giving elemental
concentrations in the unknown sample
TRACER METHOD

Radioactivity is induced into the sample by adding a


measured amount of radioactive species
ISOTOPE DILUTION

To prepare a sample for analysis, we add known mass of the


tracer to a portion of sample containing an unknown mass of
analyte
After homogenizing the sample and tracer, we isolate grams of
analyte by using a series of appropriate chemical and physical
treatments
Because our processing techniques cant distinguish between
radioactive and non radioactive forms of the analyte, the isolated
material contains both
Finally, we measure the activity of the isolated sample
ISOTOPES

Isotopes are atoms with the same number of protons or atomic


number but that have a different number of neutrons or different
mass number.
ISOTOPES
RADIOACTIVE ISOTOPES

A radioisotope is an isotope of an element that spontaneously


emits particles or radiation.
Radioisotopes can be assayed using a radio analytical method
In other cases, it is possible to bombard a non-radioactive sample
with a particle or with radiation in order to transform temporarily all
or part of the sample into a radioactive material that can be
assayed
Radioactive decay
Types of radioactive decay
Advantages of Radiochemical Techniques
RADIOACTIVE DECAY

The spontaneous transformation of an unstable atomic


nucleus into a lighter one, in which radiation is released in
the form of alpha particles, beta particles, gamma rays and
other particles.

Also known as Nuclear decay or radioactivity.


A material containing such unstable nuclei are called
radioactive.
RADIOACTIVE DECAY

Those that decay are called radioactive (or parent) isotopes; those
that are generated by decay are called radiogenic (or daughter)
isotopes.
The rate of decay of radioactive substances such as carbon 14 or
uranium is measured in terms of their half-life.
Radioactive decay involves the spontaneous transformation of one
element into another.
The only way this can happen is the change in number of protons
in the nucleus.
RADIOACTIVE DECAY

There are number of ways that this can happen and


when it does, the atom is forever changed. There is
no going back- the process is irreversible.

Some times, the product of that nuclear decay is


unstable itself and undergoes nuclear decay too.
RADIOACTIVE DECAY

U-238
(radioactive Th-234
Pa-234
isotope of (Thorium)
uranium)

14-steps

Pb-206
Decay sequence or series stops
(stable)
RADIOACTIVE DECAY

Element with 84 or more protons are unstable. They


eventually undergo decay.
Other isotopes with fewer protons in their nucleus are
also radioactive.
RADIOACTIVE DECAY

Radioactivity corresponds
to neutron/proton ratio in
atom

If ratio is too high- If ratio is too low-


isotope is neutron isotope is proton
rich and unstable rich and unstable

The neutron/proton ratio for a certain element must fall within a certain range for the
element to be stable. Thats why some isotopes of an element are stable and other
are radioactive.
TYPES OF RADIOACTIVE DECAY
Types of
Radioactive
decay

Gamma
Alpha particle Beta particle Less common
radiation
emission emission types
emission

Positron
Emission

Electron
capture

Isomeric
transition
ALPHA EMISSION
ALPHA EMISSION

An alpha particle is defined as a positively charged particle of a


helium nuclei.
It is composed of two protons and two neutrons so it regarded as
helium nuclei.
Alpha particle breaks away from the nucleus of a radioactive atom,
it has no electrons, so it has +2 charge.
Alpha particle is shown with no charge because it very rapidly
picks up two electrons and becomes a neutral helium atom---
because electrons are basically free.
Usually heavy nuclei like Uranium, Neptunium decay by alpha
emission
ALPHA EMISSION
BETA EMISSION
BETA EMISSION

A beta particle is essentially an electron thats emitted from the


nucleus
It occurs when nuclei is neutron rich
Anti neutrino is also emitted-It is without energy and charge
Actually neutron decays into a proton and electron and anti
neutrino
Thats why the mass increase after beta decay
The electron strike with nearby medium atoms to produce X-rays
which is called Bremstrahlung (Braking or slowing down radiation)
BETA EMISSION
POSITRON DECAY

In this, a proton decays into neutron, electron and neutrino


It occur in the atoms whose nuclei are Neutron deficient or Proton
rich
ELECTRON CAPTURE

It occurs in atom whose nucleus has a smaller N/Z ratio compared


to stable nucleus
An electron from extranuclear electron shells is captured, thus
transforming a proton into a neutron and emitting a neutrino
The atomic number of parent atom is reduced by 1
GAMMA EMISSION
GAMMA EMISSION

There is no mass change associated with gamma emission.


It can also be reffered as gamma radiation emission.

They are similar to X-rays- high energy and short wavelength


radiation.

If source is not known, then X-rays are indistinguishable to


Gamma rays
GAMMA EMISSION
ADVANTAGES OF RADIOCHEMICAL TECHNIQUES

Radiochemical methods are characterized by good


accuracy

Their ability to be adapted to a wide number of


applications

They minimize or even eliminate the need for


separations that are required in other analytical methods
Measurement of Radioactivity

Applications of Radiochemical Techniques


MEASUREMENT OF RADIOACTIVITY
Methods for
measurement of
radioactivity

Ionization
Liquid scintillation Radiometric
method/Gas-Filled
method techniques
Detectors

Ionization Isotope dilution


Chamber Radiometric titration Radiochromatography
method

Geiger-Muller Direct isotopic


Counter dilution analysis

Inverse isotopic
dilution analysis
IONIZATION METHOD

The Operation of a gas-filled detector is based on ionization of gas


molecules by radiation, followed by collection of the ion pairs as
current with the application of a voltage between two electrodes
Current is proportional to the applied voltage and to amount of
radiation
The difference between the two methods lies in the operating
voltage that is applied between two electrodes
IONIZATION CHAMBER

These include
Cutie-Pie counter
Dose calibrators
DOSE CALIBRATORS

Cylindrical shaped
Sealed chamber with a central well
Filled with argon and traces of halogen at high
pressure
Operating voltage is 150V
DOSE CALIBRATORS

Schematic
diagram of
Dose
Calibrator
DOSE CALIBRATORS
GEIGER-MULLER COUNTERS

Also known as Geiger-Muller tube method

Invented by Hans Geiger in 1908

Developed by Walther Muller in 1928

Detect even low level Beta and Gamma Radiation

One end of the detector is made of thin mica window that allows passage of Beta and Gamma
rays

Operating voltage is higher than the Dose calibrator-1000V


GEIGER-MULLER COUNTERS
LIQUID SCINTILLATION METHOD
It is the process in which beta radiation are transformed into
luminescence with the help of scintillating liquid that produce
scintillation
It is used for the compounds whose radiation energy is too low to
penetrate the window of Geiger-Muller Counter
Scintillation is the process or state of emitting flashes of light just
like twinkling of stars
Polash proposed this method
It is mainly used for determination of C-14
Liquid used-Benzene/ Benzene+Toulene
LIQUID SCINTILLATION METHOD

Liquid is first converted into carbon dioxide and reacted with


lithium to produce lithium carbide and fluorescence is detected
with photomultiplier tube

2CO2 + 10Li Li2C2 + 4Li2O


LIQUID SCINTILLATION METHOD
ISOTOPE DILUTION METHOD

Introduced by Havesy and Hobbie in 1932


Radiotracer is added into the sample which enable the sample to
be detected
It is mainly used for determination of inorganic compounds
ISOTOPE DILUTION METHOD

Add-organic
Small amount of solvent
Add into solvent Solution stirred
radiotracer containing
suitable reagent

Sample counted Organic phase Aliquot of organic


Radiotracer is
by Geiger Muller evaporated to phase is
extracted
Counter dryness separated
ISOTOPE DILUTION METHOD

The ideal features are:


Sample must be pure
Sample should have chemical identity
Sample should have uniform distribution
Sample should have long life
ISOTOPE DILUTION METHOD

Advantages of this method are:


Highly sensitive
Small amount can be easily handled
Less expensive
Instrumentation very simple
ISOTOPE DILUTION METHOD

It is applied for:
Elemental analysis of geological, biological, and environmental
samples
Determination of
Vitamins
Antibiotics
Aminoacids
Hormones
Study of interaction of elements in diease
Determination of total volume of the blood in human body
DIRECT ISOTOPIC DILUTION ANALYSIS

Known amount of labelled isotope is added to sample


which contains unlabeled compound
INVERSE ISOTOPIC DILUTION ANALYSIS

Known amount of non-labelled compound is added to


the sample containing unknown amount of labelled
compound
RADIOMETRIC TITRATIONS

This method is based on determination of radioactivity by the


addition of radioactive tracer.
End point is determined by sudden change in radioactivity
It requires phase separation

Example-Determination of Halides using Ag-110 as a radiotracer

AgNO3 + NaCl AgCl (ppt) + NaNO3


RADIOCHROMATOGRAPHY

This method is combination of Paper/TLC with


IEC/GC by using radioactive tracer
Spots detected by Geiger-Muller Counter or
scintillation counter
RADIOCHROMATOGRAPHY

Radiotracer is
placed in glass
Spotted with for development of
Asbestos paper chamber containing
radiotracer spot
dilute HCl and all the
paper

Place in counter Cut paper along with Paper dried in drying


For 1 hour
chamber for 50sec line chamber
APPLICATION OF RADIOCHEMICAL TECHNIQUES

Bremsstrahlung are used in radiographic procedures (X-rays)

Dose calibrators-used to measure radioactivity for formulating and dispensing


radiopharmaceuticals

C-11 (C-palmitate) is used for myocardial perfusion imaging by PET

N-13 (Ammonium ion) is used for myocardial perfusion imaging by PET

O-15 (water) is used in cerebral and myocardial perfusion studies


APPLICATION OF RADIOCHEMICAL TECHNIQUES

O-15 (CO2) is used for labeling hemoglobins and for clinical investigation of pulmonary and cardiac
malfunctions

99mTc-Sodium Pertechnetate is used for thyroid imaging

I-125 is used in I-125 serum albumin method-to measure blood volume

Gr-51 is used in Cr-51 Labeled Red blood cell method to measure blood volume

I-131 is used to treat hyperthyroidism

P-32 (P-ortho phosphate) is used to treat bone pain due to bone metastasis
REFERENCES

1. Francis Rouessac and Annick Rouessac Chemical Analysis:


Modern Instrumentation methods and Techniques. 2ND
Edition. JOHN WILEY AND SONS, LTD.

2. Gopal B. Saha Fundamentals of Nuclear Pharmacy 5TH


edition. SPRINGER

3. Gehart Freidlander, Joseph W. Kennedy, Edward S. Macias,


Julian Malcolm Miller Nuclear and Radiochemistry. 3RD
Edition. JOHN WILEY & SONS
Thanks to Respected Sir M. Sajid Hamid Akash for guiding

Thanks to all of you


WITH PROFOUND REGARDS

Rabia Nisar (13608)


Ammara Jabeen (13609)
Mustafa Ijaz (13610)

The End