Radiopharmaceuticals

Radiopharmaceuticals
inorganic Chemicals used for diagnosis as well for treatment of various disease such as cancer etc
Radiopaque contrast media:

1. Radiopharmaceuticals
isotopes, methods of nuclear radiation measurement:,
nuclear chemistry, nuclear stability, radiation dosimetry,
radioactivity, radiopaque contrast media,
radiopharmaceuticals, types of radiation emitted, types of
radioactive decay
1
Mr. Hemant P. Alhat
Asst. Professor, Pharma. Chemistry,
PES Modern College of Pharmacy (for Ladies), Moshi, Pune

2. Introduction
Nuclear Reactions vsChemical Reactions
Nuclear Reactions Chemical Reactions
1. Protons and neutrons react 1. Electrons react outside nucleus.
inside nucleus.
2. Elements transmute into other 2. The same number of each kind of
elements. atom appear in the reactants and products.
3. Isotopes react differently. 3. Isotopes react the same.
4. Independent of chemical 4. Depend on chemical combination.
combination.
5. Energy changes equal 10^8 kJ. 5. Energy changes equal 10 -10^3 kJ/mol.
6. Mass changes are detectable. 6. Mass reactants = mass products.
2

3. •Chemical reactions: Changes in the outer electronic
structure of atoms or molecules
•Nuclear reactions: study of changesin structure of nuclei
and subsequent changes in chemistry.
•Radioactive nuclei: spontaneously change structure and
emit radiation.
•Differences between nuclear and chemical reactions:
–Much larger release in energy in nuclear reaction.
–Isotopes show identical chemical reactions but different nuclear
reactions.
–Nuclear reactions not sensitive to chemical environment.
–Nuclear reaction produces different elements.
–Rate of nuclear reaction not dependent upon temperature.
3

4. Representation of atomic nucleiC
12
6
Mass number-A
Atomic number-Z C
14
6
Isotopes 12C 14C
4

5. Nucleus components
•Nucleon: any nuclear particle, e.g. protons, p, and
neutrons, n. X
A
Z
Isotopes: atoms that have identical atomic numbers
but different mass numbers
Nuclide: is a term used to identify an individual atom.
Each individual atom is called nuclide
Nuclide
5

6. Radioactivity
•Radioactivity is a nuclear reaction in which an unstable
nucleus decomposes spontaneously
•Natural radioactivity
Natural unstable nuclei decompose more stable nuclei
•Artificial radioactivity
Synthetic unstable nuclei decompose more stable nuclei
Decay
Parent
nuclei
Daughter
nuclei
6

7. 18.1 Nuclear stability and radioactive decay
•Nuclear stability
–Thermodynamic stability:the potential energy of a
nucleus as compared with sum of the potential energies
of its components protons and neutrons
–Kinetic stability: it describes the probability that a
nucleus will undergo decomposition to form a different
nucleus-a process called radioactive decay
•Stability depends upon a balance between repulsive forces
(between protons) and strong attraction forces between nuclei
7

8. •The stability of a nucleus depends mainly on A, the
mass number and Z, the atomic number. Up to the mass
number 30 or 40, a nucleus has approximately the same
numberof neutrons and protons to be stable.
•Bigger nuclei must have more neutronsthan protons.
As Zgets bigger, repulsive forces get bigger.
•When nucleus gets big enough, no neutron is enough
to keep it stable. After, Z= 82, no nuclei is stable. Such
unstable nuclei are radioactive, which means they
undergo radiations in order to become stable.
Nuclear Stability
8

9. •A nucleus having very much protons
compared to neutrons will never be stable
•This does not mean that a nucleus with
many neutrons and little protons will be
stable.
•To understand this we may look at this
graph,
Nuclear Stability
9

10. Nuclear fission
A diagram of nuclear fission, showing a neutron being absorbed by a uraniumnucleus.
This then becomes unstable, and splits into two new atoms, some energy, and some
more neutrons.
•Nuclear fission is when an atomsplits apart into smaller atoms
•It gives off a lot of energy, and is used in nuclear weaponsand nuclear
reactors
10

11. Nuclear fusion
The hydrogendeuterium-tritium(D-T) fusion reaction is being used to make Fusion power
•Nuclear fusion is the process of making a single heavy nucleus(part of an
atom) from two lighter nuclei(two "nucleuses").
•This process is called a nuclear reaction. It releases a large amount of energy.
•The nucleus made by fusion is heavier than either of the starting nuclei
•Fusion happens in the middle of starslike the Sun. Hydrogenand heliumare
fused together
11

12. Types of radiation emitted in natural radioactivity
12

13. Types of radioactive decay
radiation = attracted towards
negatively charged plate
Positively charged
radiation = attracted towards positively
charged plate
Negatively charged=1e
-

radiation = not attracted to either plate
Neutral. When emitted it does not change atomic or mass numbers
Very high energy photons; very short wavelength
. Positron is a positive electron
Positron emission is equivalent to a fall of e
-1
in
nucleus   He
4
2 e
0
1 e
0
1
13

14. NUCLEAR REACTIONS
•Radioactivity: nucleus unstable and spontaneously
disintegrates.
•Nuclear Bombardment: causes nuclei to disintegrate due
to bombardment with very energetic particles.
•Particles in nuclear reactions:1. Proton H
1
1 or p
1
1
2. Neutron n
1
0
3. Electron e
0
1 or 

0
1
4. Positron e
0
1 or 

0
1
5. Gamma ray 
0
0

14

15. 1)Total Nucleon Number (TOP VALUES) =Total number of
protons and neutrons
2)Total electric charge (BOTTOM VALUES)
Are kept the same.
Protactinium
Balancing nuclear equations
15

16. •Nuclear reaction is written maintaining mass
and charge balance.
E.g.N
14
7 C
14
6 e
0
1
+
+
16

17. Examples of adioactive decay
–Beta emission: Converts neutron into a proton by
emission of energetic electron; atomic # increases:
E.g. Determine product for following reaction:
•Alpha emission: emits He particle.
E.g. Determine product:epn
0
1
1
1
1
0 
 ?K 

0
1
40
19 He?Ra
4
2
226
88

17

18. Methods of nuclear radiation measurement:
Techniques is based upon detection & measurement of activity
Dived into 2 categories
1.Depending upon collection if IONSe.g. Geiger Muller counter (GM
counter)
2.Depending upon collection of PHOTONSe.g. Scintillation counter
Geiger Muller counter (GM counter):
In this ions r produced directly by ionizing effect of raditionon the gas molecules
In the detector
Principle is similar to ionization chamber
Used to detect alpha beta and gamma radiation
but most frequently used for beta particles.
Main difference between Gm counter and ionization chamber lies in the strength
of electric field between anode and cathode
Types of GM Counter
1.End window type : solid detecting
2.Thin wall line counter
3.Liquid counter: liquid detection
18

19. 19

20. Scintillation counter (SC ):
In this electrons r produced by photoelectric effect. The plus delivered by
the detector r amplified(if necessary) & fed to electric counting device or
scaler which records the no of pulse received or their rate of arrival
SC consists ofphosphorus and photomultiplier tube . They operate on
conduction with high voltage supply, an amplifier , a pulse height
decimator or Distinguisher & counting system
Principle:
Charged particles / gamma photons from a radioactive sources causes the
phosphorous to emit flashes of light which are made to fall on the light
sensitive cathode of Photomultiplier tube . The electrons from the cathode
travel to first dynode which them emits about 4 electrons
The electrons are collected on a plate of anode which is connected with
the high voltage supply in a such a way that electrons are received and
sudden fall in potential occurs
20

21. 21

22. Radiation Dosimetry
It refers to both animate and inanimate objects.
main interest is the effect of radiation on human and animal
There are 2 aearsof concern in radiological health std that requires description
and units of measurement.
Those 2 areas
1.Exposure dose (ED): refers to the quantity of potentially harmful radiation or
the amount of radiation available for interaction with some target materials
Unit of measurement for this (ED) radiation is roentgen (R)
1 R is the qty of X or gamma radiation that will produce sufficention pairs to have
1 electrostatic unit (esu) of charge of ether sign in 1 cc of dry air at std temp
and pressure (STP)
1 R = 2.58×10
−4
C/kg(from 1 esu≈ 3.33564×10
−10
C and the standard
atmosphere air density of ~1.293kg/m³)
ED mesearuedas a dose rate at particular distance from the radiation sources
dose may be repotedin unit (r/hr/m/rhm)
2. Absorbed dose: refers to specifying the absorbed dose is rad(radiation
absorbed dose)
Describes potential damage to biological tissues to different types of radiation.
This term is known as the relative biological effectiveness or RBE
22

23. Name SymbolRadiation Equivalent units
types
Roentgen r /R x,γ 1 R = 2.58×10
−4
C/kg(from 1 esu
≈ 3.33564×10
−10
C and the standard
atmosphere air density of
~1.293kg/m³)
Radiation absorbed dose rad all 100ergs/g absorbed by
any medium
Relative biological RBE α 10-20
effectiveness β 1
x, γ 1
Roentgen equivalent rem all dose in rads x RBE
to man
1 rem = 0.01 Sv = 10 mSv = 10000 μSv
Radiation dosimetry units:
23

24. Radiopaquecontrastmedia: e.g.bariumsulphateBaSO
4
•Thisarethechemicalcompoundcontainingelementsofhighatomicno.whichwillstopthe
passageofxrays
•Suchcompoundsareusedasdiagnosticaidsinradiology
•Radiologyinvolvesuseofxrayswhichareshortwavelengthelectromagneticradiation(EMR)in
theimagingorshadingofvariousinternalorganstructure
•bone&teethareonlythetypesoftissuesthatarecapableofarrestingthepassageofxraysbecoz
chemicalconstituentsofbone&teethwhichgivetheirabilitytostoptheradiationaslargeconc.Of
calcium&phosphorus&softtissuebeinglessdense&composedprimarilyofC,H&Owhichhave
relativelylowinatomicnumberduetothissofttissue/skin/organsappearonlyasshadows
•Themostcommonradiopaquesarebrown&iodine
•BARIUMisveryusefulradiopaquemedia(inorganiccompound),thatexhibitsomesolubility.
Althoughbarium&iodinedonothavehighatomicno.buttheyaremostlyincorporatedinto
moleculeswithlowtoxicity.
•IODINEcompoundarecovalentlyc\bondedtoorganiciodides,arenonionic&organicmolecule
usuallyhassameaffinityfororgansystemtobestudied.generallyrouteofadministrationis
throughIVinjectionuseforxraysexaminationofkidney,liverbloodvessels,heart,&brain.
•Theiropacitytoxraydependantupontheirconcentrationintheorgantobestudied 24

25. NeutronActivationMethods
Activationmethodscanbeclassifiedinseveralas
DestructiveMethods
Mostcommonactivationprocedure
Involvessolutionofaknownamountoftheirradiatedsample
Followedbyseparationoftheanalytefrominterferences.
Theisolatedmaterialisthencountedforitsbetaorgammaactivity.
Conventional neutron activation analysis involves irradiation of a std containing a
known mass w. of the analyte simultaneously and in the same neutron flux as ~e
sample. Insofar as the activity !hat results IS proportional to mass, and provided
also that " the other components of the sample do .not . produce detectable
radioactivity, the Weight w• of the element in the sample is given by
Wx = Rx XWs
Rs
where Ax. and As. are the Counting rate of the sample and standard.
Ws is weight od Std
Adequateresolution depend upon complexity of sample the presence or absence of
elements which produce gamma rays of about the same energy as that of the
element of interest
25

26. Improvements in resolving power,
Greatly broadened the scope of the nondestructive method.
However selective and sensitive activation methods are still based upon
isolation of the analyte.
Great Advantage of the nondestructive approach
Simplicityin terms of sample handling and
Speed; to be sure, the required instrumentation is more complex.
Minimumoperating time
26

27. NonDestructiveMethods
•AnalyteareseparatedfromtheothercomponentsPrior/beforecounting
•AknownamtofirradiatedsamplesisdisssolvedandanalyteSEPARATED
•ByPPTnEXTRACTION,IONEXCHANGECHROMATOGRAPHY
•Isolatedmaterialisthencountedforitsgammaandbetaactivity
Wx = Rx XWs
Rs
where Ax. and As. are the Counting rate of the sample and standard.
Ws is weight od Std
27

28. Applications for NAA
Archaeology
The use of neutron activation analysis to characterize archaeological specimens
(e.g., pottery, obsidian, chert, basalt and limestone)
Soil Science
Many agricultural processes and their consequences, such as fertilization and
herbicidal and pesticidal control, are influenced by surface and sub-surface
movement, percolation and infiltration of water.
Geology
Analysis of rock specimens by neutron activation analysis assists geochemists in
research on the processes involved in the formation of different rocks through the
analysis of the rare earth elements
Epidemiology
In-situ Radiotracers for Dosage-Form Testing
Over the last several years there has been a growing interest in the use of in-situ
radiotracers to test new pharmaceuticals and dosage forms being developed for
commercial distribution.
Thyroid Cancer Study
characterizing the nail as a biologic monitor for iodine; and to measure iodine in
nails obtained in a nested case-control study of thyroid cancer. In these subjects,
the use of iodine-containing contrast agents can confound analytical
interpretations of any biologic monitor
28

29. IsotopedilutionMethod(IDM)
radiochemicalmethodofanalysisformeasuringthemass
andquantityofanelementinasubstance.Theprocedure
involvesaddingtoasubstanceaknownquantityofa
radioisotopeoftheelementtobemeasuredandmixingit
withthestableisotopeoftheelement.
Asampleisthentakenfromthemixtureandanalyzed.
Bymeasuringtheamountofradioactiveisotopeandthe
amountofstableisotopepresentanddeterminingtheratioof
theseamounts,boththequantityandmassoftheelementcan
beascertained.
IDMisemployedchieflyinanalyticalchemistryinsituationsin
whichPRECISEquantitativeanalysisbyconventionalmeans
isdifficult.Certainkindsofgeophysicalinvestigationsalso
requireitsuse,asindeterminingtheoccurrenceand
distributionoftraceelementsinrocksamplesandmeteorites.
29

30. Application
Used for determination of more than 30 elements
Used for determination of organic, biochemical elements
Used for determination of vitamin D, B12, sucrose, insulin
30

31. Wr the species is found to have an activity
Wr wt of isoalted purified and mixture
Wo wt of radioactivity
31

32. RADIOCHEMCIAL PURITY
The amount of r in SPECIFIED CHEICMAL FORM expressed as a % of total
Radioactivity (R)
e.g. iodine-125
125
I iIodine and
125
IO
3
Iodate
Radiochemical Purity can be changed with TIMEdue to
decomposition
Radionuclide Purity
RP associates with three imp points as
Half life
Pure Radioactivity emission
To Be produced Daily
Isotopes
Stable isotopes
Sponaneoulsy undergo changes
half life upto billion years
Un Stable isotopes
Do not change
Exist for LT 1 sec
32

33. RADIOACTIVE DECAY PROCESS
Thedisintegrationofradioactiveisotopesproducesenergeticparticlesand
electromagneticradiation(EMR).i.e.asAlphabetaandgammaradiations
Decay Law
RadioactivedecayisacompletelyRANDOMPROCESS.
Thus,whilenopredictionCanbemadeconcerningthelifetimeofanindividual
nucleus,thebehaviorofalargeensembleoflikenucleicanbedescribedbythe
expression
-dN/dt = λ N
where Nrepresents the number of radioactive
nuclei in the sample at time tand
λ is th characteristicdecay for radioisotope.
rearrangingthisequationandintegratingovertheintervalbetweent=0(initial
time)andt=t(endtime)
In N/ No = -λt
Thehalf-lifeofaradioactiveisotopeisdefinedasthetime
requiredforthenumberofatomstodecreasetoone-halfofits
originalquantity;i.e.forNtobecomeequaltoNo/2.SubstitutionofNo/2forNin
Equationgiven
33

34. t 1/2= 0. 693 / λ
t ½ (half life) ranges from sec to billion
years
34

35. Radiopharmaceuticals:
A radioactive drugs admistrated safely to human for Diagnostic
and Therapeuticresponse
•Tagging of Compound
•R isotope r Chemically Identical with their
stable isotope. They r used to tag compound
•Tagging of comp r followed through
•Analytical scheme
•Industrial scheme
•Biological scheme
•Tagged with atom i.e. non exchangeable with similar atom
in other compound under normal condition
•In Biological Investigation –Purity of isolated material is
very imp
35

36. •Certain R is isolated-due to compound itself
(high specificity) & not due to some minor
containments
•Usual chemical methods of purification tagged
compound to be carried out –on fractions of
specific activities to be determined
•Lack of consistency of specific activity is
evidences of R-Chemical impurities
•
36

37. Applications
•IDM for analyzing the
mixture of amino acid
•Determination of Vitamins
•NAA determination of
impurities
•Analysis of trace elements
•Analysis of geological
species as rocks and earth
•Analysis of Archeological
artifacts
•De3rtemiation of volume
of water in body
•Iodine-125 (60 d) used in cancer
brachytherapy (prostate and brain).
•Iodine 123 used as antineoplastic.
•Treatment of Thyroid Disease with
Iodine 131
•Cobalt 60 used as antineoplastic.
•Gold1 94 used as antineoplasatic.
•Phosphorous-32used for palliative
treatment of bone metastases
•Chromium 51 Used to label RBC
•Iron 59used in studies of iron
metabolism in the spleen.
•Rubidium 86 used for determination
of myocardial blood flow.
37

38. 38
Reference
•nsdl.niscair.res.in
•Gastrointestinal Agents Dr. Mymoona
Akhter, 17-7-2007
•Inorganic, Medicinal and Pharmaceutical
Chemistry by J. H. Block, E. B. Roche, Indian
edition, Varghese Publication.