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Radiopharmaceutical
Himanshu Joshi
B.R.Nahata College of Pharamacy,
Mandsaur University, Mandsaur, MadhyaPradesh
hjhimanshujoshi61@gmail.com
Subject – Organic Chemistry
Subject Code – BP-101T
Overview
1. Atom, Atomic no. , Mass no. , Nucleus, isotope, isobars
2. Radioactive Substance–Alpha, Beta and Gamma rays
3. Unit of radioactivity, Disintegration rate, Half Life
4. Measurement Method of Radioactivity-
• Ionization Chamber
• Proportional Counter
• Geiger Muller Counter
• Scintillation Counter
• Autoradiography
• Solid State Detector
5. Radiopharmaceutical Product & it’s formulation
• NaI Solution
• NaI Capsule
• Iodinated Human Serum Albumin
• Rose Bengal I131
6. Application of Radiopharmaceuticals
ATOM
An atom consist of a small central nucleus
composed of proton and neutrons surrounded by
electrons.
e- (electron) + p+ (Proton) + Neutron
–ve charge +ve charge Neutral
Atom
• Atomic Number :- Number of p+ present in
the atom - always constant.
e.g. 6C, 15P
• Mass Number :- Total number of p+ +
number of neutron - may be vary due to
change in number of neutrons.
• Nuclide [atom, elements] – Particular species
characterised by its atom number & mass
number.
e.g. 12C
• Isotope :-
- Same atomic number
- Different mass number
e.g. 126C, 136C, 106C
• Isobars :-
- Different atomic number
- Same atomic mass
e.g. 146C, 147N
• If the no. of neutron is equal to or slightly greater
than the no. of p+
Nucleus is stable
• If the no. of neutron is less or significantly greater
than the no. of p+
Nucleus is unstable
P+ (Proton) N0 (Neutron) Nucleus (Nuclei)
6 4 Unstable
6 5 Unstable
6 6 Stable
6 7 Stable
6 8 Unstable
Radionuclei or Radioisotopes
• Unstable nucleus undergo spontaneous
nuclear changes in order to achieve stability
by emitting radiation is known as radionuclei
or radioisotope.
Types of
Radionuclei
Natural
238U, 226Ra
Artificial
32P, 131I
Radioactive Substance
• Substance that emits radiation or rays or particle.
• Radiation is not influenced by temperature,
pressure, concentration, catalyst.
Types of
radioactive rays
α Alpha rays β Beta rays γ Gamma rays
Alpha Rays
• Least penetration power.
• High ionizing power.
• +ve charge (carry two +ve charge).
• a particle are similar to Hellium nuclei having mass
4amu.
• Deflected by strong magnetic field.
• Emitted specially from heavy metals.
• All a particles are having same energy.
• When a radioactive element emits a particle resulting
atom nucleus will have two +ve charge less than
original nucleus or its atomic no. Less than 2 units
compared to original.
• Mass no. :- less than 4 amu as compared to
original
226 88 Ra 222 86 Rn + 4 2 He
B- Rays
Types of B rays
Electrically +ve particle
Known as
POSITRONS
Electrically –ve particle
Known as
NEGATRONS
B- Rays : General Properties
• Having greater penetrating power than a and less
than r gamma rays.
• Having less ionizing power than a and greater than
gamma rays.
• The emission of b particles from element doesn’t
alter atomic mass but alter atomic number and is
converted to element with next higher atomic
number.
e.g.
i) 146C 147N + B- [Negatron]
ii) In some cases Neutrons are transformed into
protons with beta emission.
1 0n 11P + B+ [Positron]
r- Rays : General Properties
• Emits by nucleus.
• Highest penetration power.
• Highest ionizing power.
• They are having same characteristics as that of
electromagnetic wave called X-ray have.
• They have no mass or charge.
• X-rays are emitted from planetary e- but r rays
emitted from nucleus.
• r rays produced during the disintegration of
radioactive substances along with b radiation and
during nuclear fission.
• when r rays reacts with matter, it behaves as discrete
packet [Quanta] of energy, they are called Photon.
Unit of radioactivity :- Curie ‘C’
• Penetration Power
a<B<r
• Ionizing Power
a>B>r
Basic property of all rays
• Curie is defined as “quantity of any radioactive substances
which undergoes the same number of disintegration in
unit time as of 1gm of radium” (equal to 3.7 X 1010
dis/sec).
• millicurie :- 1 X 10-3 of curie = 3.7 X 107 disintegation/sec
• microcurie :- 1 X 10-6 of curie = 3.7 X 104 disintegation/sec
dN/dt N
dN/dt = λ N
• dn/dt = rate of change in number of radioactive
nuclei with time.
• λ = Decay constant [probability of disintegration in
unit time for a particular radionuclei]
• N = Number of radioactive nuclei present at a
particular time.
Disintegration Rate
• The time taken for half of the radioactive nucleus
to disintegrate is known as half life.
t1/2 = 0.693/ λ
1) Half life of I131 = 8 days
2) Half Life of P32 = 14.3 days
Half life
1. Ionisation Chamber
2. Proportional Counter
3. Geiger Muller Counter
4. Scintillation Counter
5. Autoradiography
6. Solid State Detectors
Measurement Method of Radioactivity
Ionisation Chamber
• Construction :- Ionisation chamber consist of
chambers filled with gas and fitted with two
electrode kept at different electrical
potential. [50-100 volts for each cm of
distance between two electrode]
• Current measuring device to indicates flow of
current.
• Working :- Radiation ionization of gas
molecules cause emission of e- rreveals
change in electric current.
• These are modified ionization chamber.
• In this applied potential ionisation of primary e-
cause thunderous bursting or production of more
free e- which get carried into anode.
• For each primary e- liberated much more
additional e- get liberated the current pulse
through electrical circuit is greatly amplified.
• The voltage range over which gas amplification
(ionisation) occurs called proportional region and
the counters working in this region are called
proportional counter.
Proportional Counter
• Don’t need high gain amplifier.
• It can detect a, B and r radiations.
• Construction :- Posses cylindrical cathode [1-2cm
in diameter] along the centre which is wire anode.
The space filled with special gas mixture.
Geiger Muller Counter [Most Popular]
Special Gas Mixture
Contains
Gas
(Which is readily
ionised)
Quenching Vapour
To prevent spurious pulses that may get
produced due to +ve ions reaching to the
cathode.
To absorb photons generated by excited
atoms.
Design & Construction of Geiger Muller Counter
depends on the purpose for which they are required:-
A. For Solid :- End Window Type
B. For Liquids :- 10ml Angular Space
C. For Liquids :- Capacity 5ml
D. To count medium & high energy B and gamma particle
counting :- Glass Walled Counter
Example of Quenching agents :- Chlorine, Bromine,
Ethylalcohol, Ethylformate
Diagrams of Geiger Muller Counter
Operation or Working of Geiger Muller Counter :-
1. In order to operate GM counter, a source of high
voltage together with low gain amplifier & sealing
unit for registering the pulses are needed.
2. In order to reduce counting rate without any source
in position i.e. “Background” counting rate, the GM
counter has been mounted in lead shield.
3. It’s having shelves to hold a source in one or more
position & for holding absorbers between the
counter and source.
4. When the voltage and counter gets raised, no
region of pulses will be observed until a certain
voltage gets reached [Starting Voltage].
Operation or Working of Geiger Muller Counter :-
5. The counting rate increases rapidly to the
threshold and at 150-200 volts or more, the
counting rates sensitivity constant.
6. At the same time size of individual pulses get
increased with voltage.
7. So, that at higher voltage there has been tendency
for spurious discharges get initiated. It has been
one of the reason or cause for stop of plateau.
Scintillation Counter
Construction :- Consist of a cell, a photomultiplier
tube which is coupled with phosphor fluorescent
material to convert scintillation into electrical
pulses, amplifier and scalar.
Scintillation Counter
Working :-
Phosphor – Crystal of sodium iodide [NaI]
Which gets activated with some amount thallium to increase the degree of fluroscence
R radiation passing through a small window enters the crystal [NaI (Tl)]
Give rise small flash of light brought to photomultiplier tube which it turn detect flash
Amplifier amplifies signals and convert into an electrical impulse
Record directly by scalar
Scintillation Counter
• Used for detecting 3H, 14C
Types
Inorganic
E.g. CSI (Ti), CSI (Na), LiI (Ea)
Organic
E.g. Anthracene
Autoradiography
• Useful in detecting & determining r radiation.
Administration of radioactive substance to
animal
After sufficient time lapse for
localisation
The tissue is removed and embedded in
paraffin
Cut into thin section by microtone
Keep in contact with photographic emulsion
Radioactive atom present in cut section emitting particle
which darken photographic emulsion
After sufficient time of exposure emulsion has been
developed and fixed
Solid State Detectors :-
Advantage Disadvantage
• High resolution • High Cost
• Compactness • Low temperature to be maintained
• Easy interpretation
Types of Solid State Detectors
Semiconductor
Detectors
Photographic
Emulsion
Cherenkov
Detectors
A. Semiconductor Detectors :-
• These are diode of n & p semiconductors.
• Semiconductor :-)
o n-type = e- rich
o p-type = e- deficient
• Application of reverse bias across the diode transport of e-
towards the n- end that of holes p-end, thus creating an
intrinsic region with no charge carriers.
• The absorption of incident radiation result in formation of e-
- n+ pairs which moves under the influence of applied electric
field.
• The collection of e-s across a resistance leads to voltage
pulse which are proportional to incident energy.
E.g.
• Lithium drifted Ge (Germanium)
• Silicon Detecctors (Ge[Li]), (Si[Li])
• High Purity Ge (HPGe)
B. Photographic Emulsion:-
• Ordinary photographic films consist of emulsion
of silver halide grains suspended in gelatine
matrix & supported with glass or cellulose
acetate film.
• Ionizing radiation sensitize the silver halide
grains which remain impact in definite period
until they are developed.
C. Cherenkov Detectors:-
• Radiation strikes on particles and then fast
charged particle pass through optically
transparent medium cause emission of light.
Radiopharmaceutical Product & it’s Formulation
• Suitable for oral or IV administration.
131Th52
131I53Th [Uranium fission or neutron
bombardment of Th]
• Half life of I131 = 8.08 days
1. Sodium Iodide (NaI131) Solution :-
Radiopharmaceutical Product & it’s Formulation
 Properties :-
1. Clear colourless solution.
2. But over a period of time both glass & solution may darken
due to the effect of radiation. pH= 7.5-9
3. IV administration solution use Benzylalcohol as
preservatives.
4. In solution also add Na2S2O3 [Sodium thisulphate] as
reducing agent to prevent oxidation of NaI in aqueous
solution.
5. Solution contains not less than 90% or not more than 110%
of the labelled amount of Iodine-131 (I131).
6. Other radioisotope should be absent.
1. Sodium Iodide (NaI131) Solution :-
Radiopharmaceutical Product & it’s Formulation
 Preparation :-
• Prepared by evaporating alcoholic solution of NaI131 directly
on the wall of capsule or on the inert capsule filling material.
 Packaging & Storage :-
• Single dose or multiple dose container is used.
• Container wash with Sodium bisulphate [0.8%] , [0.25%] NaI
and then with H2O until last rinsing has been neutral to
litmus.
 Radioactivity :- Detect by Scintillation Counter.
 Uses :-
• Diagnosis for thyroid functioning.
• In Hyperthyroidism and Thyroid Carcinoma.
2. Sodium Iodide (NaI) Capsule :-
Radiopharmaceutical Product & it’s Formulation
 Preparation :-
• Prepared by refluxing Rose Bengal acid with radioiodine (I131)
produced by action of an oxidizing agent on sodium radio
iodide for about 15-20 hours.
• Rose Bengal I131 is produced precipitate it with acid wash with
H2O convert in Na++ salt by treatment with NaOH and
sterilised by autoclave & filteration.
Storage :-
• Preserved at refrigerated temperature formulated with
propylene glycol.
Use:-
• To detect Liver function.
3. Rose Bengal I131:-
Radiopharmaceutical Product & it’s Formulation
 Preparation :-
• Involves reaction of Albumin in Glycine buffer with I131 which
is released from NaI-NaIO3 mixture and the process occur at
pH- 9.3.
• 3 atoms of I131 gets incorporated with per molecule of iodine,
then purified by passing the reaction mixture over an anionic
exchange resins, sterilised and filtration by Millipore filter.
Storage :-
• At refrigerated temperature.
Use:-
• To investigate CVS functions.
4. Iodinated Human Serum Albumin:-
Application of Radiopharmaceutical
1. Therapeutics
2. Diagnosis
3. Sterilization
4. Research
5. Other specific radioisotope
Thanks
Readers

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Radiopharmaceutical

  • 1. Radiopharmaceutical Himanshu Joshi B.R.Nahata College of Pharamacy, Mandsaur University, Mandsaur, MadhyaPradesh hjhimanshujoshi61@gmail.com Subject – Organic Chemistry Subject Code – BP-101T
  • 2. Overview 1. Atom, Atomic no. , Mass no. , Nucleus, isotope, isobars 2. Radioactive Substance–Alpha, Beta and Gamma rays 3. Unit of radioactivity, Disintegration rate, Half Life 4. Measurement Method of Radioactivity- • Ionization Chamber • Proportional Counter • Geiger Muller Counter • Scintillation Counter • Autoradiography • Solid State Detector 5. Radiopharmaceutical Product & it’s formulation • NaI Solution • NaI Capsule • Iodinated Human Serum Albumin • Rose Bengal I131 6. Application of Radiopharmaceuticals
  • 3. ATOM An atom consist of a small central nucleus composed of proton and neutrons surrounded by electrons. e- (electron) + p+ (Proton) + Neutron –ve charge +ve charge Neutral Atom
  • 4. • Atomic Number :- Number of p+ present in the atom - always constant. e.g. 6C, 15P • Mass Number :- Total number of p+ + number of neutron - may be vary due to change in number of neutrons. • Nuclide [atom, elements] – Particular species characterised by its atom number & mass number. e.g. 12C
  • 5. • Isotope :- - Same atomic number - Different mass number e.g. 126C, 136C, 106C • Isobars :- - Different atomic number - Same atomic mass e.g. 146C, 147N
  • 6. • If the no. of neutron is equal to or slightly greater than the no. of p+ Nucleus is stable • If the no. of neutron is less or significantly greater than the no. of p+ Nucleus is unstable P+ (Proton) N0 (Neutron) Nucleus (Nuclei) 6 4 Unstable 6 5 Unstable 6 6 Stable 6 7 Stable 6 8 Unstable
  • 7. Radionuclei or Radioisotopes • Unstable nucleus undergo spontaneous nuclear changes in order to achieve stability by emitting radiation is known as radionuclei or radioisotope. Types of Radionuclei Natural 238U, 226Ra Artificial 32P, 131I
  • 8. Radioactive Substance • Substance that emits radiation or rays or particle. • Radiation is not influenced by temperature, pressure, concentration, catalyst.
  • 9. Types of radioactive rays α Alpha rays β Beta rays γ Gamma rays
  • 10. Alpha Rays • Least penetration power. • High ionizing power. • +ve charge (carry two +ve charge). • a particle are similar to Hellium nuclei having mass 4amu. • Deflected by strong magnetic field. • Emitted specially from heavy metals. • All a particles are having same energy. • When a radioactive element emits a particle resulting atom nucleus will have two +ve charge less than original nucleus or its atomic no. Less than 2 units compared to original.
  • 11. • Mass no. :- less than 4 amu as compared to original 226 88 Ra 222 86 Rn + 4 2 He
  • 12. B- Rays Types of B rays Electrically +ve particle Known as POSITRONS Electrically –ve particle Known as NEGATRONS
  • 13. B- Rays : General Properties • Having greater penetrating power than a and less than r gamma rays. • Having less ionizing power than a and greater than gamma rays. • The emission of b particles from element doesn’t alter atomic mass but alter atomic number and is converted to element with next higher atomic number. e.g. i) 146C 147N + B- [Negatron] ii) In some cases Neutrons are transformed into protons with beta emission. 1 0n 11P + B+ [Positron]
  • 14. r- Rays : General Properties • Emits by nucleus. • Highest penetration power. • Highest ionizing power. • They are having same characteristics as that of electromagnetic wave called X-ray have. • They have no mass or charge. • X-rays are emitted from planetary e- but r rays emitted from nucleus. • r rays produced during the disintegration of radioactive substances along with b radiation and during nuclear fission. • when r rays reacts with matter, it behaves as discrete packet [Quanta] of energy, they are called Photon.
  • 15. Unit of radioactivity :- Curie ‘C’ • Penetration Power a<B<r • Ionizing Power a>B>r Basic property of all rays • Curie is defined as “quantity of any radioactive substances which undergoes the same number of disintegration in unit time as of 1gm of radium” (equal to 3.7 X 1010 dis/sec). • millicurie :- 1 X 10-3 of curie = 3.7 X 107 disintegation/sec • microcurie :- 1 X 10-6 of curie = 3.7 X 104 disintegation/sec
  • 16. dN/dt N dN/dt = λ N • dn/dt = rate of change in number of radioactive nuclei with time. • λ = Decay constant [probability of disintegration in unit time for a particular radionuclei] • N = Number of radioactive nuclei present at a particular time. Disintegration Rate
  • 17. • The time taken for half of the radioactive nucleus to disintegrate is known as half life. t1/2 = 0.693/ λ 1) Half life of I131 = 8 days 2) Half Life of P32 = 14.3 days Half life
  • 18. 1. Ionisation Chamber 2. Proportional Counter 3. Geiger Muller Counter 4. Scintillation Counter 5. Autoradiography 6. Solid State Detectors Measurement Method of Radioactivity
  • 20. • Construction :- Ionisation chamber consist of chambers filled with gas and fitted with two electrode kept at different electrical potential. [50-100 volts for each cm of distance between two electrode] • Current measuring device to indicates flow of current. • Working :- Radiation ionization of gas molecules cause emission of e- rreveals change in electric current.
  • 21. • These are modified ionization chamber. • In this applied potential ionisation of primary e- cause thunderous bursting or production of more free e- which get carried into anode. • For each primary e- liberated much more additional e- get liberated the current pulse through electrical circuit is greatly amplified. • The voltage range over which gas amplification (ionisation) occurs called proportional region and the counters working in this region are called proportional counter. Proportional Counter
  • 22. • Don’t need high gain amplifier. • It can detect a, B and r radiations. • Construction :- Posses cylindrical cathode [1-2cm in diameter] along the centre which is wire anode. The space filled with special gas mixture. Geiger Muller Counter [Most Popular] Special Gas Mixture Contains Gas (Which is readily ionised) Quenching Vapour To prevent spurious pulses that may get produced due to +ve ions reaching to the cathode. To absorb photons generated by excited atoms.
  • 23. Design & Construction of Geiger Muller Counter depends on the purpose for which they are required:- A. For Solid :- End Window Type B. For Liquids :- 10ml Angular Space C. For Liquids :- Capacity 5ml D. To count medium & high energy B and gamma particle counting :- Glass Walled Counter Example of Quenching agents :- Chlorine, Bromine, Ethylalcohol, Ethylformate
  • 24. Diagrams of Geiger Muller Counter
  • 25. Operation or Working of Geiger Muller Counter :- 1. In order to operate GM counter, a source of high voltage together with low gain amplifier & sealing unit for registering the pulses are needed. 2. In order to reduce counting rate without any source in position i.e. “Background” counting rate, the GM counter has been mounted in lead shield. 3. It’s having shelves to hold a source in one or more position & for holding absorbers between the counter and source. 4. When the voltage and counter gets raised, no region of pulses will be observed until a certain voltage gets reached [Starting Voltage].
  • 26. Operation or Working of Geiger Muller Counter :- 5. The counting rate increases rapidly to the threshold and at 150-200 volts or more, the counting rates sensitivity constant. 6. At the same time size of individual pulses get increased with voltage. 7. So, that at higher voltage there has been tendency for spurious discharges get initiated. It has been one of the reason or cause for stop of plateau.
  • 27. Scintillation Counter Construction :- Consist of a cell, a photomultiplier tube which is coupled with phosphor fluorescent material to convert scintillation into electrical pulses, amplifier and scalar.
  • 28. Scintillation Counter Working :- Phosphor – Crystal of sodium iodide [NaI] Which gets activated with some amount thallium to increase the degree of fluroscence R radiation passing through a small window enters the crystal [NaI (Tl)] Give rise small flash of light brought to photomultiplier tube which it turn detect flash Amplifier amplifies signals and convert into an electrical impulse Record directly by scalar
  • 29. Scintillation Counter • Used for detecting 3H, 14C Types Inorganic E.g. CSI (Ti), CSI (Na), LiI (Ea) Organic E.g. Anthracene
  • 31. • Useful in detecting & determining r radiation. Administration of radioactive substance to animal After sufficient time lapse for localisation The tissue is removed and embedded in paraffin Cut into thin section by microtone Keep in contact with photographic emulsion Radioactive atom present in cut section emitting particle which darken photographic emulsion After sufficient time of exposure emulsion has been developed and fixed
  • 32. Solid State Detectors :- Advantage Disadvantage • High resolution • High Cost • Compactness • Low temperature to be maintained • Easy interpretation Types of Solid State Detectors Semiconductor Detectors Photographic Emulsion Cherenkov Detectors
  • 33. A. Semiconductor Detectors :- • These are diode of n & p semiconductors. • Semiconductor :-) o n-type = e- rich o p-type = e- deficient • Application of reverse bias across the diode transport of e- towards the n- end that of holes p-end, thus creating an intrinsic region with no charge carriers. • The absorption of incident radiation result in formation of e- - n+ pairs which moves under the influence of applied electric field. • The collection of e-s across a resistance leads to voltage pulse which are proportional to incident energy. E.g. • Lithium drifted Ge (Germanium) • Silicon Detecctors (Ge[Li]), (Si[Li]) • High Purity Ge (HPGe)
  • 34. B. Photographic Emulsion:- • Ordinary photographic films consist of emulsion of silver halide grains suspended in gelatine matrix & supported with glass or cellulose acetate film. • Ionizing radiation sensitize the silver halide grains which remain impact in definite period until they are developed.
  • 35. C. Cherenkov Detectors:- • Radiation strikes on particles and then fast charged particle pass through optically transparent medium cause emission of light.
  • 36. Radiopharmaceutical Product & it’s Formulation • Suitable for oral or IV administration. 131Th52 131I53Th [Uranium fission or neutron bombardment of Th] • Half life of I131 = 8.08 days 1. Sodium Iodide (NaI131) Solution :-
  • 37. Radiopharmaceutical Product & it’s Formulation  Properties :- 1. Clear colourless solution. 2. But over a period of time both glass & solution may darken due to the effect of radiation. pH= 7.5-9 3. IV administration solution use Benzylalcohol as preservatives. 4. In solution also add Na2S2O3 [Sodium thisulphate] as reducing agent to prevent oxidation of NaI in aqueous solution. 5. Solution contains not less than 90% or not more than 110% of the labelled amount of Iodine-131 (I131). 6. Other radioisotope should be absent. 1. Sodium Iodide (NaI131) Solution :-
  • 38. Radiopharmaceutical Product & it’s Formulation  Preparation :- • Prepared by evaporating alcoholic solution of NaI131 directly on the wall of capsule or on the inert capsule filling material.  Packaging & Storage :- • Single dose or multiple dose container is used. • Container wash with Sodium bisulphate [0.8%] , [0.25%] NaI and then with H2O until last rinsing has been neutral to litmus.  Radioactivity :- Detect by Scintillation Counter.  Uses :- • Diagnosis for thyroid functioning. • In Hyperthyroidism and Thyroid Carcinoma. 2. Sodium Iodide (NaI) Capsule :-
  • 39. Radiopharmaceutical Product & it’s Formulation  Preparation :- • Prepared by refluxing Rose Bengal acid with radioiodine (I131) produced by action of an oxidizing agent on sodium radio iodide for about 15-20 hours. • Rose Bengal I131 is produced precipitate it with acid wash with H2O convert in Na++ salt by treatment with NaOH and sterilised by autoclave & filteration. Storage :- • Preserved at refrigerated temperature formulated with propylene glycol. Use:- • To detect Liver function. 3. Rose Bengal I131:-
  • 40. Radiopharmaceutical Product & it’s Formulation  Preparation :- • Involves reaction of Albumin in Glycine buffer with I131 which is released from NaI-NaIO3 mixture and the process occur at pH- 9.3. • 3 atoms of I131 gets incorporated with per molecule of iodine, then purified by passing the reaction mixture over an anionic exchange resins, sterilised and filtration by Millipore filter. Storage :- • At refrigerated temperature. Use:- • To investigate CVS functions. 4. Iodinated Human Serum Albumin:-
  • 41. Application of Radiopharmaceutical 1. Therapeutics 2. Diagnosis 3. Sterilization 4. Research 5. Other specific radioisotope