The document discusses radiopharmaceuticals and the production of radioisotopes. It covers key topics such as: 1) The definition of a radiopharmaceutical as a special class of radiochemical formulation suitable for administration to patients for diagnosis or therapy. 2) Methods for producing radioisotopes including nuclear fission, which produces lighter, more stable nuclides, and neutron activation, where stable nuclei absorb neutrons to form radioactive nuclei. 3) Factors to consider in the design of new radiopharmaceuticals like compatibility between the radioisotope and molecule, the charge, size and stability of the radiolabeled molecule.

1. Presented By:
Lone Vidya R.
Government College Of
Pharmacy, Aurangabad.
12/26/12 1

2. Outline of
presentation
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Page 2

3. Radiopharmacy studies related to the
Radiopharmacy studies related to the
pharmaceutical, chemical,
pharmaceutical, chemical,
physical,biochemical, and biological
physical,biochemical, and biological
aspects of radiopharmaceuticals.
aspects of radiopharmaceuticals.
A Radiopharmaceuticala special class of
A Radiopharmaceuticala special class of
radiochemical formulation having high
radiochemical formulation having high
purity, sterility and apyrogenicity,
purity, sterility and apyrogenicity,
suitable for administration to human
suitable for administration to human
patients either orally or intravenously,
patients either orally or intravenously,
either for diagnosis or therapy
either for diagnosis or therapy
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4. Evolution Of Nuclear Medicine
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5. 12/26/12 5

6. 12/26/12 6

7. TERMINOLOGY
TERMINOLOGY
Isotopes
Isotopes
Atoms of the same element with different atomic mass
Atoms of the same element with different atomic mass
numbers
numbers
e.g. carbon-12, carbon-13 and carbon-14
e.g. carbon-12, carbon-13 and carbon-14
Nuclide
Nuclide
is a type of atom whose nuclei have specific numbers of
is a type of atom whose nuclei have specific numbers of
protons and neutrons
protons and neutrons
Notation of a nuclide= AAEZ
Notation of a nuclide= EZ
e.g. = 235U92
e.g. = 235U92
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8. Types Of Nuclides
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9. RADIONUCLIDE
RADIONUCLIDE
(Radioisotopes))
(Radioisotopes
An atom with an unstable nucleus,
An atom with an unstable nucleus,
characterized by excess energy
characterized by excess energy
available to be imparted either to
available to be imparted either to
A newly created radiation particle
A newly created radiation particle
within the nucleus or via internal
within the nucleus or via internal
conversion.
conversion.
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10. CLASSIFICATION OF RADIONUCLIDE
Stability class No. of nuclides
Radioactive non-primordial, but naturally occurring on 51
Earth
Radioactive synthetic (half-life < 1 hour) >2400
Theoretically stable to all but proton decay 90
Radioactive synthetic (half-life > 1 hour). Includes most 562
useful radiotracers
Energetically unstable to one or more known decay 163
modes.
Radioactive primordial nuclides 35
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11. Radioactivity
The process in which an unstable isotope undergoes changes until a
stable state is reached and in the transformation emits energy in the
form of radiation (alpha particles, beta particles and gamma rays).
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12. 12/26/12 12

13. RADIATION MEASUREMENT
The basic unit for quantifying radioactivity (i.e. describes the rate at
which the nuclei decay).
Curie (Ci):
Curie (Ci), named for the famed scientist Marie Curie
Curie = 3.7 x 1010 atoms disintegrate per second (dps)
Millicurie (mCi) = 3.7 x 107 dps
Microcurie (μCi) = 3.7 x 104 dps
Becquerel (Bq):
A unit of radioactivity. One Becquerel is equal to 1
disintegration per second.
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14. Radioactive decay
Radioactive decay
The process in which an unstable atomic
nucleus spontaneously loses energy by
emitting ionizing particles and radiation.
Mode Of Radioactive Decay
Naturally……….combination of α, β
and γ emission.
Artificially……….spontaneous
fission, neutron emission and even
proton and heavy-ion emission.
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15. RADIOACTIVE DECAY LAW
RADIOACTIVE DECAY LAW
The rate of decay (number of disintegrations per unit time)
The rate of decay (number of disintegrations per unit time)
is proportional to N, the number of radioactive nuclei in the
is proportional to N, the number of radioactive nuclei in the
sample ……
sample ……
dN/ dt ∞ -λN……
dN/ dt ∞ -λN……
Large λ =rapid decay;
Large λ =rapid decay;
small λ =slow decay.
small λ =slow decay.
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16. Types of decay 1- Alpha particle
2- Beta particle
3- Gamma ray
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17. Type of Radiation Alpha particle Beta particle Gamma ray
Symbol or
Charge +2 -1 0
Speed slow fast Very fast
Ionising ability high medium 0
Penetrating power low medium high
Stopped by: paper aluminium lead
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18. Properties of an Ideal Diagnostic
Properties of an Ideal Diagnostic
Radioisotope
Radioisotope
Easy Availability
Easy Availability
Types of Emission
Types of Emission
Energy of Gamma Rays
Energy of Gamma Rays
Photon Abundance
Photon Abundance
Target to Non target Ratio
Target to Non target Ratio
Effective Half-life
Effective Half-life
Patient Safety
Patient Safety
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19. EASY
EASY
AVAILABILITY
AVAILABILITY
The radiopharmaceutical should be easily
The radiopharmaceutical should be easily
produced, inexpensive, and readily
produced, inexpensive, and readily
available in any nuclear medicine
available in any nuclear medicine
facility
facility
TYPES OF Pure Gamma Emitter
Pure Gamma Emitter
EMISSION (Alpha & Beta Particles are non
(Alpha & Beta Particles are non
imageable & Deliver High Radiation
imageable & Deliver High Radiation
Dose.)
Dose.)
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20. ENERGY OF
ENERGY OF
GAMMA
GAMMA
RAYS
RAYS
For diagnostic studies the radionuclide must emit aaƔ radiation with an
For diagnostic studies the radionuclide must emit Ɣ radiation with an
energy preferably between 30 and 300 kev. Below 30 kev, Ɣ rays are
energy preferably between 30 and 300 kev. Below 30 kev, Ɣ rays are
absorbed by tissue
absorbed by tissue
Ideal: 100-250 kev
Ideal: 100-250 kev
e.g. 99mTc, 123I, 111In
e.g. 99mTc, 123I, 111In
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21. PHOTON
PHOTON
ABUNDANCE
ABUNDANCE
Should be high
Should be high
to minimize
to minimize
imaging time.
imaging time.
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22. Target to Non
Target to Non It should be high to:
Maximize the
target Ratio
target Ratio efficacy of diagnosis.
Minimize the
radiation dose to the
patient.
An ideal radiopharmaceutical should have
An ideal radiopharmaceutical should have
all the above characteristics to provide
all the above characteristics to provide
maximum effcacy in the diagnosis of
maximum effcacy in the diagnosis of
diseases and aaminimum radiation
diseases and minimum radiation
dose to the patient.
dose to the patient.
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23. EFFECTIVE HALF-LIFE
1. It should be short enough to minimize the radiation dose to
patients and long enough to perform the procedure.
2. Ideally 1.5 times the duration of the diagnostic procedure.
3. Example: For a Bone Scan which is a 4-h procedure,
99mTc- phosphate compounds with an effective half-life of
6 h are the ideal radiopharmaceuticals.
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24. DESIGN OF NEW RADIOPHARMACEUTICALS
General
Considerations
1. The method of preparation should be simple, easy, and
1. The method of preparation should be simple, easy, and
reproducible, and should not alter the desired property of the
reproducible, and should not alter the desired property of the
labeled compound.
labeled compound.
2. Optimum conditions of temperature, pH, ionic strength, and molar
2. Optimum conditions of temperature, pH, ionic strength, and molar
ratios should be established and maintained for maximum effcacy
ratios should be established and maintained for maximum effcacy
of the radiopharmaceutical.
of the radiopharmaceutical.
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25. Factors Influencing the Design of New
Factors Influencing the Design of New
Radiopharmaceuticals
Radiopharmaceuticals
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26. COMPATIBILITY
When aalabeled compound is to be prepared, the first criterion to consider is
When labeled compound is to be prepared, the first criterion to consider is
whether the label can be incorporated into the molecule to be labeled.
whether the label can be incorporated into the molecule to be labeled.
 This may be assessed from aaknowledge of the chemical properties of the two
 This may be assessed from knowledge of the chemical properties of the two
partners.
partners.
 For example, 111In ion can form coordinate covalent bonds, and DTPA is aa
 For example, 111In ion can form coordinate covalent bonds, and DTPA is
chelating agent containing nitrogen and oxygen atoms with lone pairs of
chelating agent containing nitrogen and oxygen atoms with lone pairs of
electrons that can be donated to form coordinated covalent bonds.
electrons that can be donated to form coordinated covalent bonds.
Therefore, when 111In ion and DTPA are mixed under appropriate
Therefore, when 111In ion and DTPA are mixed under appropriate
physicochemical conditions, 111In-DTPA is formed and remains stable for aa
physicochemical conditions, 111In-DTPA is formed and remains stable for
long time.
long time.
12/26/12 26

27. CHARGE OF
THE MOLECULE
The charge on aaradiopharmaceutical
The charge on radiopharmaceutical
determines its solubility in various
determines its solubility in various
solvents.
solvents.
 The greater the charge, the higher the
 The greater the charge, the higher the
solubility in aqueous solution.
solubility in aqueous solution.
Nonpolar molecules tend to be more
Nonpolar molecules tend to be more
soluble in organic solvents and lipids
soluble in organic solvents and lipids
12/26/12 27

28. SIZE OF THE
SIZE OF THE
MOLECULE
MOLECULE
It is an important determinant in its
It is an important determinant in its
absorption in the biologic system.
absorption in the biologic system.
 Larger molecules (mol. wt. >~60, 000)
 Larger molecules (mol. wt. >~60, 000)
are not filtered by the glomeruli in the
are not filtered by the glomeruli in the
kidney.
kidney.
 This information should give some clue
 This information should give some clue
as to the range of molecular weights of the
as to the range of molecular weights of the
desired radiopharmaceutical that should be
desired radiopharmaceutical that should be
chosen for aagiven study.
chosen for given study.
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29. PROTEIN BINDING
Almost all drugs, radioactive or not, bind to plasma proteins to variable
degrees.
Protein binding is greatly influenced by a number of factors, such as the
charge on the radiopharmaceutical molecule, the pH, the nature of protein,
and the concentration of anions in plasma.
111In-chelates exchange 111In with transferrin to form 111In-transferrin.
Protein binding the tissue distribution and plasma clearance of a
radiopharmaceutical and its uptake by the organ of interest
12/26/12 29

30. SOLUBILITY
SOLUBILITY
For injection, the radiopharmaceutical should be in
aqueous solution at a pH compatible with blood pH (7.4).
The ionic strength and osmolality of the agent should
also be appropriate for blood.
The radiopharmaceutical 111In-oxine is highly soluble in
lipid and is therefore used specifically for labeling
leukocytes and platelets.
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31. STABILITY
STABILITY
It must be stable both in vitro and in vivo.
It must be stable both in vitro and in vivo.
 In vivo breakdown of aaradiopharmaceutical results in undesirable
 In vivo breakdown of radiopharmaceutical results in undesirable
biodistribution of radioactivity.
biodistribution of radioactivity.
For example, dehalogenation of radioiodinated compounds gives
For example, dehalogenation of radioiodinated compounds gives
free radioiodide, which raises the background activity in the clinical
free radioiodide, which raises the background activity in the clinical
study.
study.
 Temperature, pH, and light the stability of many compounds and
 Temperature, pH, and light the stability of many compounds and
the optimal range of these physicochemical conditions must be
the optimal range of these physicochemical conditions must be
established for the preparation and storage of labeled compounds.
established for the preparation and storage of labeled compounds.
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32. PRODUCTION OF
RADIOISOTOPES
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33. Nuclides with a mass larger
Nuclear than about 130 amu
spontaneously split apart to
Fission form lighter, more stable,
nuclides.
The half-life for the
spontaneous fission
of 238U is 1016 years
By irradiating samples of
heavy nuclides with slow-
moving thermal neutrons it
is possible to induce fission
reactions.
E.g:-99Mo (which decays to
99
Tcm), 131I, and 133Xe.
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34. More than 370 daughter
nuclides with atomic masses
between 72 and 161 amu are
formed in the thermal-neutron-
induced fission of 235U,
including the two products
12/26/12 34

35. NEUTRON
ACTIVATION
Neutrons produced by the fission of uranium
Neutrons produced by the fission of uranium
in aanuclear reactor can be used to create
in nuclear reactor can be used to create
radionuclides by bombarding stable target
radionuclides by bombarding stable target
material placed in the reactor.
material placed in the reactor.
Process involves capture of neutrons by
Process involves capture of neutrons by
stable nuclei
stable nuclei
98
Mo + n → 99Mo + γ
50
Cr + n → 51Cr + γ
31
P + n → 32P + γ
32
S + n → 32P + p
12/26/12 35

36. The produced radioisotope is typically an
isotope of the target element, therefore
chemical separation is not possible.
This means that the (N,γ) produced
radionuclide are not carrier-free.
12/26/12 36

37. CHARGED
PARTICLE INDUCED
REACTIONS
•Radionuclides may be produced by
bombarding target materials with
charged particles in particle
accelerators such as cyclotrons.
•Based on the use of accelerators.
Charged particles like protons,
deuterons or alphas are accelerated to
energies between 1 to 100 MeV and
bombard a target material.
12/26/12 37

38. Cyclotron
Cyclotron
 cyclotron consists of :
Two flat hollow objects called Dees.
The dees are part of an electrical circuit.
On the other side of the dees are large magnets that
(drive) steer the injected charged particles (protons,
deutrons, alpha and helium) in a circular path.
The charged particle follows a circular path until
the particle has sufficient energy that it passes out of
the field and interact with the target nucleus. 12/26/12 38

39. RADIONUCLIDE
RADIONUCLIDE
A system for holding
A system for holding GENERATORS
GENERATORS
the parent in such aaway
the parent in such way
that the daughter can be
that the daughter can be
easily separated for
easily separated for
clinical use is called aa
clinical use is called
radionuclide generator
radionuclide generator Principle:
Principle:
A long-lived parent
A long-lived parent
radionuclide is allowed to
radionuclide is allowed to
decay to its short-lived
decay to its short-lived
daughter radionuclide and the
daughter radionuclide and the
latter is chemically separated in
latter is chemically separated in
aaphysiological solution.
physiological solution.
Example:
Example:
technetium-99m, obtained from
technetium-99m, obtained from
aagenerator constructed of
generator constructed of
molybdenum-99 absorbed to an
molybdenum-99 absorbed to an
alumina column
alumina column
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40. 99Mo/99mTc
Generator
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41. Various techniques, for the preparation of
radionuclide generators
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42. 12/26/12 42

43. 12/26/12 43

44. 12/26/12 44

45. List Of Radiopharmaceuticals
Radiopharmaceutical Trade Name Primary Uses
Carbon-14 Urea Pytest Detection of H Pylori
Cobalt-57 cyanocobalamin Rubratope Schilling test
Cobalt -57 & -58 Dicopac Schilling test
cyanocobalamin
Chromium-51sodium chromate Chromitope (Bracco)
Mallinckrodt Cr-51 for labeling RBCs
Fluorine-18 FDG positron emission tomography imaging
Fluorine-18 Florbetapir Amyvid Beta amyloid plaque PET imaging for
Alzheimer's disease
Gallium-67 Neoscan (GE) soft-tissue tumor and inflammatory process
DuPont Ga-67 imaging
Mallinckrodt Ga-67
Indium-111 chloride Indiclor (Nycomed) for labeling monoclonal antibodies and
Mallinckrodt In-111Cl peptides (OncoScint & Octreoscan)
12/26/12 45

46. Indium-111 pentetate (DTPA) Indium DTPA In 111 imaging of CSF kinetics
Indium-111 oxyquinoline Indium-111 oxine for labeling leukocytes and platelets
(oxine)
Indium-111 Capromab monoclonal antibody for imaging prostate
ProstaScint
pendetide cancer
Indium-111 Imciromab monoclonal antibody for diagnosis of
Myoscintnot on market
pentetate myocardial necrosis
Indium-111 pentetreotide Octreoscan imaging of neuroendocrine tumors
Indium-111 satumomab OncoScint CR/OV imaging of metastatic disease associated
pendetide not on market with colorectal and ovarian cancer
I-123 sodium iodide thyroid imaging & uptake
MallinckrodtAmersham
I-123 Iobenguane (MIBG) neuroendocrine tumor imaging
Adreview
I-125 iothalamate Glofil measurement of glomerular filtration
I-125 human serum albumin Isojex plasma volume determinations
(RISA)
12/26/12 46

47. Tositumomab & Iodine I 131 Bexxar Treatment of Non-Hodgkin's Lymphoma
Tositumomab
I-131 iodohippurate Hippuran; renal imaging and function studies
HipputopeDiscontinued
products
I-131 (Univ of Michigan) adrenal imaging
iodomethylnorcholesterol(NP-
59)
I-131 I-131 MIBG imaging of pheochromocytomas and
metaiodobenzylguanidine(MIB neuroblastomas
G)
Krypton-81m gas (from Rb-81 Discontinued pulmonary ventilation imaging
generator)
P-32 chromic phosphate Phosphocol�P32 therapy of intracavitary malignancies
P-32 sodium phosphate therapy of polycythemia vera
Rubidium-82 (from Sr-82/Rb- Cardio-Gen-82 positron emission tomography imaging
82 generator)
12/26/12 47

48. Tc-99m Arcitumomab CEA-Scanoff the market monoclonal antibody for colorectal cancer
Tc-99m albumin colloid Microlite discontinued imaging of RES (liver/spleen)
Tc-99m bicisate (ECD) Neurolite cerebral perfusion imaging
Tc-99m Depreotide Neotectoff the market somatostatin receptor-bearing pulmonary
masses
Tc-99m disofenin (DISIDA) Hepatolite - CIS hepatobiliary imaging
Tc-99m exametazine (HMPAO) Ceretec cerebral perfusion imaging
Tc-99m Gluceptate DraximageMallinckrodt renal imaging
off the market
Tc-99m Human Serum Albumin imaging of cardiac chambers
(HSA)
Tc-99m Fanolesomab Tc-99m NeutroSpecoff monoclonal antibody for infectious imaging
the market
12/26/12 48

49. Applications Of
Radiopharmaceuticals
As an aid in the diagnosis of
Treatment of disease disease
Radiolabelled Molecules Disease
Chromic Phosphate P32 For Lung, Ovarian, Uterine, And
Prostate Cancers
Sodium Iodide I 131 Thyroid Cancer
Samarium Sm 153 Cancerous Bone Tissue
Sodium Phosphate P 32 Cancerous Bone Tissue And Other
Types Of Cancers
Strontium Chloride Sr 89 Cancerous Bone Tissue
12/26/12 49

50. As an aid in the diagnosis of disease
(diagnostic radiopharmaceuticals)
e.g.
e.g.
1.51 Cr-EDTA for measuring glomerular filtration
1.51 Cr-EDTA for measuring glomerular filtration
rate.
rate.
2. e.g.99m TC-methylene di phosphonate (MDP) used
2. e.g.99m TC-methylene di phosphonate (MDP) used
in bone scanning).
in bone scanning).
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2. The radiopharmacy;a technologist’s guide; editors by
Suzanne dennan; chapter 1; ppno. 2-12
Suzanne dennan; chapter 1; no. 2-12
3. Advances in medical radiation imaging for cancer diagnosis and treatment,
3. Advances in medical radiation imaging for cancer diagnosis and treatment,
Nuclear technology review 2006, IAEA, (2006) pp. 110-127.
Nuclear technology review 2006, IAEA, (2006) pp. 110-127.
4. Beneficial uses and production of radioisotopes. 2004 update. Nea/iaea
4. Beneficial uses and production of radioisotopes. 2004 update. Nea/iaea
Joint publication. Oecd 2005.
Joint publication. Oecd 2005.
5. Development of radionuclide generators for biomedical applications, by
5. Development of radionuclide generators for biomedical applications, by
Rubel chakravarty bhabha atomic research centre
Rubel chakravarty bhabha atomic research centre
6. www. Wikipedia.com
6. www. Wikipedia.com 12/26/12 51

52. 12/26/12 52