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Radiopharmaceuticals
Presented by
Sonali S Gadge
Lecturer, M.Pharm (QA)
P R Patil , Institute of Pharmacy, Talegaon(SP), Dist- Wardha.
INTRODUCTION
 Radiopharmaceuticals are unique medicinal
formulations containing radioisotopes which are used
in major clinical areas for diagnosis and for therapy.
 The facilities and procedures for the production, use,
storage of radiopharmaceuticals by subject to licensing
by national and/or regional authorities.
 Additional regulations may apply for issues such as
transportation or dispensing of radiopharmaceuticals.
• All substances made of atoms.
• These have electrons around the outside (negatively
charged), and the nucleus in the middle.
• The nucleus consists of protons (positively charged)
and neutrons (neutral).
• The atomic number of an atom is the number of
protons in it’s nucleus.
• The atomic mass is the number of protons + neutrons
in it’s nucleus.
 Isotopes of an atom have the same number of protons, but a
different number of neutrons.
 Radiopharmaceuticals are medicinal formulations containing
radioisotopes which are safe for administration in humans for
diagnosis and for therapy.
Composed of two parts : Radionuclide + Pharmaceutical
 Nuclide defines as any species of atom characterized by a
specific number of neutrons and protons within the nucleus.
 Radiation(emission of energy) refers to particles or waves
coming from the nucleus of the atom (radioisotope or
radionuclide) through which the atom attempts to attain more
stable configuration.
eg. Uranium
Radioactivity :
• Many heavy elements like uranium, thorium, radium & their compounds
emits radiation spontaneously.
• These radiations can penetrate through solid materials, can ionize gases,
produce a glow on zinc sulphide paint or affect the photographic plates.
• The substances which emits radiations are called radioactive substances
& the phenomenon of spontaneous & continuous emission of such
radiations is called as radioactivity.
• It was discovered accidentally by French Scientist Henry Becquerel.
• Radiopharmaceuticals are used in medicines.
• It is used to treat cancerous tumors, to diagnose thyroid disorders &
other metabolic disorders including brain function.
Types of Radioactivity
1. Natural radioactivity :
Nuclear reactions occur spontaneously
2. Artificial/Induced radioactivity :
Radioactivity produced in a substance by bombardment with
high-speed particles such as protons or neutrons.
Radioactive Rays
Radioactive radiations are composed of three important rays α, β,γ which differ very much in their
nature and properties.
α rays :
• These rays or particles are positively charged.
• It consists of two positive charges and has mass which is nearly four times
that of ‘H’ atom.
• These are heavy, slow moving, and their penetration power is low (you can
stop them just a sheet of paper.)
• The penetrating power of α rays is least as compaired to other emissions.
• Α particles are made of 2 protons and 2 neutrons.
• We can write them as 4α2 or 4 He2 because they are the same as Helium
nucleus.
• Because of low penetrating power of α particles,
elements which emit these do not find any use in
biological applications as they can not penetrate tissue.
• During the emission of α particles from a radioactive
element, atomic number decreases by 2 units and mass
number decreases by 4 units.
230Th
90
226Ra88 + 4H2
β Particles
These rays or particles are negatively charged, this means that these particles are
same as an electron.
We can write them as β- or e- because they are same as an electron.
They have been two types-
1. Electrically positive particles called “Positrons”.
2. Electrically negative particles called “Negatrons”
They are having greater penetrating power than that of the α rays.
β particles are also having negligible mass, about 1/1836 that of ‘H’ atom.
Β particles have less ionizing power than α particles.
β particles are having the much more penetrating power than α particles.
Thus, these particles are able to pass through an aluminium foils.
During the emission of β particles from a radioactive elements, atomic number
increases by 1 unit & there is no change in mass number.
14C6
14N7 + β-
γ rays
• These are neutral i.e. do not carrying charge .
• They have more penetrating power than α & β rays.
• They have same character as that of very short
electromagnetic waves called x rays.
• The particles of these rays has negligible mass.
• As they do not have any mass, their ionizing power is also
poor.
• They are not affected by magnetic field & having the speed
of light.
Property α- rays β - rays γ rays
1. Nature
a) Charge Each particle carry
two units of +
charge.
β particle carry
one unit of
negative charge.
These rays are
neutral i.e. do not
carry charge.
b) Mass Each particle has a
mass of 4 a.m.u.
Each particle has a
mass of 5.5 × 10-4
a.m.u.
The particle of
these rays has
negligible mass.
c) Nature Helium nuclie or
He2+
Electron
2. Velocity 3×107 ms-1 2.97×108 ms-1 3×108 ms-1
3. Penetration
Power
Small Large 100 times
that of α - rays
Very large 1000
times that of α rays
4. Ionising power High Low 1/100th of α
rays
Very poor
Isotopes
• Atoms of an element which have the same atomic number but
have different mass number, are called Isotopes.
• In other words, isotopes are atoms of the same element whose
nuclei contain the same number of protons but different number of
neutrons.
• When the radioactive isotopes undergo nuclear reactions and they
produce α,β,γ particles.
• The original nuclide is called the parent and the product is termed
as Daughter Nuclide.
• This phenomenon of nuclear changes is termed as disintegration
or radioactive decay.
Stability of Isotopes
• The naturally occuring nuclides are having favourable ratio of protons and
neutrons in most elements .
• Any deviation from the normal ratio i.e. increase or decrease in the number of
protons alters the atomic number & stability of the nucleus.
• Thus, the stable ratio for potassium is 1:1.115.
• If one more proton is added to the nucleus, this ratio is disturbed and the nuclide
becomes unstable.
• Similarly, any addition or removal of a proton from the nucleus of iodine causes
instability.
• Most isotopes of elements with Z no. 83 or less are stable & are described as
stable isotopes.
• However, some of the naturally occuring nuclides with Z no. above 83 whether
naturally occuring or artificially prepared, are unstable.
Units of Radioactivity :
1. Curie : The basic unit of radioactivity is “Curie”, which is
symbolised as “C”.
It may be defined as the quantity of any radioactive substance
which undergo same number of disintegration in unit time.
1 curie = 3.7× 1010 dps
The subunits have been termed as milicurie (mc) & microcurie (µ)
1 Milicurie = 3.7 ×107 dps
1 Milicurie = 3.7 × 104 dps
2. Roentgen (R): It is the unit of exposure.
1 R = 2.58 × 10-4 C Kg-1
3. RAD (Radiation Absorbed Dose): It is the unit absorbed dose.
1 RAD = 10-2 JKg-1
Bacquerel (Bq)- It is defined as one disintegration per second.
106 Bq = 1 RAD
3.7× 1010 Bq = 1C
Half life of Radioelement -
The half period is defined as the time required for a radioactive isotopes to decay to one half of it’s
initial value.
It is denoted by t ½.
It is given by the equation – t ½ = 0.0693/ʎ
Where ʎ = decay constant
Each radioactive isotopes has its own characteristics of half life.
Shorter the half life period of an element, greater is the number of disintegrating atoms & hence
greater is it’s radioactivity.
The half life period of different radioelememnts vary widely ranging from fraction of seconds to
millions of years.
Half lives of various radionucleides vary considerably-
Eg. Polonium – 212 has half life of 3×10-7 seconds
Iodine 131 – 8 days
Uranium 238 - 4.5×104 years
zinc – 65 – 150 days
sodium – 22- 26 years
• The half life of a nuclide will decide it’s utility in
medicine.
• Too short t ½ will be inconvenient for setting up
satisfactory experiments.
• Too long half life is an absolute property of nuclide & is
unaffected by chemical or biological conditions.
Measurement of Radioactivity
• To measure the radiations of α, β, γ particles, many techniques involving
detection & counting of individual particles or photons have been available.
• The gas ionisation devices include pulse ionisation chamber, Proportional
Counter & Geiger- Muller Counter.
• Scintillation methods are especially employed for counting gamma radiations.
• The method selected for the measurement of radioactivity depends upon the
extent of energy & penetrability of radiation.
1. Ionisation chambers :
• These are available in various shapes and sizes.
• An ionisation chamber consists of chambers filled with gas & fitted with two
electrodes kept at different electrical potentials & measuring device to indicate
the flow of electric current.
• Radiation brings about ionisation of gas molecules or ions which cause
emission of electrons, which in turn reveals the changes in electrical current.
2. Proportional Couunters –
• These are the modified ionisation chambers in which an applied potential
ionisation of primary electrons causes thunderous bursting or production of
more free electrons which get carried to the anode.
• As for each primary electron liberated, much more additional electrons get
liberated, the current pulse through the electrical circuit is amplified.
• The voltage range over which the gas amplification (ionisation) occurs is called
proportional region, the counters working in this region are called Proportional
Counters.
3. Geiger – Muller Counters –
• These are the still most population detectors.
• They do not need use of a high gain amplifier and they can detect α, β, γ radiations.
• G-M counter is having ionising gas & also having quenching vapour whose
functions have been –
1. To prevent the spurious pulses that may be produced due to positive ions reaching the
cathode.
2. To absorb the photons emitted by excited atoms & molecules returning to their
ground state.
• Both Chlorine & Bromine are generally employed as quenching agent.
• Ethyl alcohol & ethyl formate are used as organic quenching agents.
•
Operation of Geiger – Muller Counters
• A G-M probe unit is regarded as an electrical switch, in which each pulse may
make to current to pass to scaler to counting unit for recording the number of
pulses.
• In order to operate the G-M counters, a source of high voltage, together with a
low-gain amplifier & sealing unit of registering the pulses are needed.
• When the voltage on the current gets raised, no registration of pulses will be
observed until a certain voltage gets raised.
• The counting rate increases rapidly to the threshold & at 150-200 V or more, the
counting rates becomes sensibly constant.
• At the same time size of individual pulses gets increased with voltage, so that at
higher voltages there has been a tendency for spurious discharges to get
initiated.
• It has been one of the causes for slope of plateau.
 Scintillation Counter
• Alpha, beta, gamma can be detected by scintillation counters.
• Ionizing radiation strikes certain substances like phosphurus.
• A flash of light given out. Flash is collected by photomultiplier tube, produces
electric impulses.
• Impulse on amplification is recorded by scaler.
• Counter consists of a scintillation crystal coupled with photomultiplier tube, an
amplifier and scaler.
• For gamma radiation, phosphurus in crystals sodium iodide activated with about 1%
thalium. Enhances the degree of flurescence.
• Γ radiation passing through a small window enter the crystal, produces small flash
of light.
• This is brought to photomultiplier tube, detects flash and amplifies it into an
electrical impulse. Impulse recorded by scaler.
 Radio Opaque contrast media
• Radio opaque contrast media (ROCM) are diagnostic drugs used
for the enhancement of radiographic (x-ray) examinations. Radio
opaque substances are those compounds, both organic and
inorganic, that have the property of casting a shadow on x- ray
films. These substances has the ability to stop the passage of x-
rays and hence appear opaque on the x-ray examination. Such
compounds and their preparations are called as x-ray contrast
media.
• Inorganic compounds like barium sulphate and some bismuth
compounds are useful as radio opaque contrast media for
diagnostic use. These are administered either as orally or
intravenously . These compounds are useful for examination of
gastrointestinal tract, kidney, liver, gall bladder and bile duct,
blood vessel of heart, etc.
 Barium Sulphate
Molecular formula: BaSO4 Molecular wt.: 233.43g/mol
Properties:
It is fine white, odourless, tasteless, bulky powder and free from grittiness.
The salt is insoluble in water, organic solvent, dilute acids and alkalies.
It is soluble in concentrated sulphuric acid.
It can be solubalised with sulphuric acid or by fusing it with alkali carbbonates. Once it converted
to carbonates, it reacts with acids easily.
Preparation:
Barium sulphate is obtained in commercial amounts from the mineral barite, after mining and
processing. The processing of the impure barite involves heating it with coke (carbon) to form
the water-soluble barium sulfide (BaS), which is then separated from the impurities and
reacted with sulphuric acid to give the pure barium sulphate product :
BaS + H2SO4 BaSO4 + H2S
Another method to obtain pure barium sulphate is by reacting barium carbonate or barium
chloride with sulphuric acid.
BaCl2 + H2SO4 BaSO4 + HCl
 Uses
• Barium sulphate is widely used as a radio-opaque agent or x-ray contrast agent
to diagnose gastrointestinal medical conditions.
• It is administered by enema before x-ray examination in the form barium meal
to make the intestine tract opaque to x-rays, so that it could be photographed.
• Barium meal – it is suspension of barium sulphate.
• Storage - It is stored in a well closed container.
To learn something new, you need to
try new things and not be afraid to
be wrong –
Roy T. Bennett

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Radiopharmaceuticals: Diagnosis and Therapy with Radioisotopes

  • 1. Radiopharmaceuticals Presented by Sonali S Gadge Lecturer, M.Pharm (QA) P R Patil , Institute of Pharmacy, Talegaon(SP), Dist- Wardha.
  • 2. INTRODUCTION  Radiopharmaceuticals are unique medicinal formulations containing radioisotopes which are used in major clinical areas for diagnosis and for therapy.  The facilities and procedures for the production, use, storage of radiopharmaceuticals by subject to licensing by national and/or regional authorities.  Additional regulations may apply for issues such as transportation or dispensing of radiopharmaceuticals.
  • 3. • All substances made of atoms. • These have electrons around the outside (negatively charged), and the nucleus in the middle. • The nucleus consists of protons (positively charged) and neutrons (neutral). • The atomic number of an atom is the number of protons in it’s nucleus. • The atomic mass is the number of protons + neutrons in it’s nucleus.
  • 4.  Isotopes of an atom have the same number of protons, but a different number of neutrons.  Radiopharmaceuticals are medicinal formulations containing radioisotopes which are safe for administration in humans for diagnosis and for therapy. Composed of two parts : Radionuclide + Pharmaceutical  Nuclide defines as any species of atom characterized by a specific number of neutrons and protons within the nucleus.  Radiation(emission of energy) refers to particles or waves coming from the nucleus of the atom (radioisotope or radionuclide) through which the atom attempts to attain more stable configuration. eg. Uranium
  • 5. Radioactivity : • Many heavy elements like uranium, thorium, radium & their compounds emits radiation spontaneously. • These radiations can penetrate through solid materials, can ionize gases, produce a glow on zinc sulphide paint or affect the photographic plates. • The substances which emits radiations are called radioactive substances & the phenomenon of spontaneous & continuous emission of such radiations is called as radioactivity. • It was discovered accidentally by French Scientist Henry Becquerel. • Radiopharmaceuticals are used in medicines. • It is used to treat cancerous tumors, to diagnose thyroid disorders & other metabolic disorders including brain function.
  • 6. Types of Radioactivity 1. Natural radioactivity : Nuclear reactions occur spontaneously 2. Artificial/Induced radioactivity : Radioactivity produced in a substance by bombardment with high-speed particles such as protons or neutrons.
  • 7. Radioactive Rays Radioactive radiations are composed of three important rays α, β,γ which differ very much in their nature and properties. α rays : • These rays or particles are positively charged. • It consists of two positive charges and has mass which is nearly four times that of ‘H’ atom. • These are heavy, slow moving, and their penetration power is low (you can stop them just a sheet of paper.) • The penetrating power of α rays is least as compaired to other emissions. • Α particles are made of 2 protons and 2 neutrons. • We can write them as 4α2 or 4 He2 because they are the same as Helium nucleus.
  • 8. • Because of low penetrating power of α particles, elements which emit these do not find any use in biological applications as they can not penetrate tissue. • During the emission of α particles from a radioactive element, atomic number decreases by 2 units and mass number decreases by 4 units. 230Th 90 226Ra88 + 4H2
  • 9. β Particles These rays or particles are negatively charged, this means that these particles are same as an electron. We can write them as β- or e- because they are same as an electron. They have been two types- 1. Electrically positive particles called “Positrons”. 2. Electrically negative particles called “Negatrons” They are having greater penetrating power than that of the α rays. β particles are also having negligible mass, about 1/1836 that of ‘H’ atom. Β particles have less ionizing power than α particles. β particles are having the much more penetrating power than α particles. Thus, these particles are able to pass through an aluminium foils. During the emission of β particles from a radioactive elements, atomic number increases by 1 unit & there is no change in mass number. 14C6 14N7 + β-
  • 10. γ rays • These are neutral i.e. do not carrying charge . • They have more penetrating power than α & β rays. • They have same character as that of very short electromagnetic waves called x rays. • The particles of these rays has negligible mass. • As they do not have any mass, their ionizing power is also poor. • They are not affected by magnetic field & having the speed of light.
  • 11.
  • 12. Property α- rays β - rays γ rays 1. Nature a) Charge Each particle carry two units of + charge. β particle carry one unit of negative charge. These rays are neutral i.e. do not carry charge. b) Mass Each particle has a mass of 4 a.m.u. Each particle has a mass of 5.5 × 10-4 a.m.u. The particle of these rays has negligible mass. c) Nature Helium nuclie or He2+ Electron 2. Velocity 3×107 ms-1 2.97×108 ms-1 3×108 ms-1 3. Penetration Power Small Large 100 times that of α - rays Very large 1000 times that of α rays 4. Ionising power High Low 1/100th of α rays Very poor
  • 13. Isotopes • Atoms of an element which have the same atomic number but have different mass number, are called Isotopes. • In other words, isotopes are atoms of the same element whose nuclei contain the same number of protons but different number of neutrons. • When the radioactive isotopes undergo nuclear reactions and they produce α,β,γ particles. • The original nuclide is called the parent and the product is termed as Daughter Nuclide. • This phenomenon of nuclear changes is termed as disintegration or radioactive decay.
  • 14. Stability of Isotopes • The naturally occuring nuclides are having favourable ratio of protons and neutrons in most elements . • Any deviation from the normal ratio i.e. increase or decrease in the number of protons alters the atomic number & stability of the nucleus. • Thus, the stable ratio for potassium is 1:1.115. • If one more proton is added to the nucleus, this ratio is disturbed and the nuclide becomes unstable. • Similarly, any addition or removal of a proton from the nucleus of iodine causes instability. • Most isotopes of elements with Z no. 83 or less are stable & are described as stable isotopes. • However, some of the naturally occuring nuclides with Z no. above 83 whether naturally occuring or artificially prepared, are unstable.
  • 15. Units of Radioactivity : 1. Curie : The basic unit of radioactivity is “Curie”, which is symbolised as “C”. It may be defined as the quantity of any radioactive substance which undergo same number of disintegration in unit time. 1 curie = 3.7× 1010 dps The subunits have been termed as milicurie (mc) & microcurie (µ) 1 Milicurie = 3.7 ×107 dps 1 Milicurie = 3.7 × 104 dps 2. Roentgen (R): It is the unit of exposure. 1 R = 2.58 × 10-4 C Kg-1 3. RAD (Radiation Absorbed Dose): It is the unit absorbed dose. 1 RAD = 10-2 JKg-1
  • 16. Bacquerel (Bq)- It is defined as one disintegration per second. 106 Bq = 1 RAD 3.7× 1010 Bq = 1C Half life of Radioelement - The half period is defined as the time required for a radioactive isotopes to decay to one half of it’s initial value. It is denoted by t ½. It is given by the equation – t ½ = 0.0693/ʎ Where ʎ = decay constant Each radioactive isotopes has its own characteristics of half life. Shorter the half life period of an element, greater is the number of disintegrating atoms & hence greater is it’s radioactivity. The half life period of different radioelememnts vary widely ranging from fraction of seconds to millions of years. Half lives of various radionucleides vary considerably- Eg. Polonium – 212 has half life of 3×10-7 seconds Iodine 131 – 8 days Uranium 238 - 4.5×104 years zinc – 65 – 150 days sodium – 22- 26 years
  • 17. • The half life of a nuclide will decide it’s utility in medicine. • Too short t ½ will be inconvenient for setting up satisfactory experiments. • Too long half life is an absolute property of nuclide & is unaffected by chemical or biological conditions.
  • 18. Measurement of Radioactivity • To measure the radiations of α, β, γ particles, many techniques involving detection & counting of individual particles or photons have been available. • The gas ionisation devices include pulse ionisation chamber, Proportional Counter & Geiger- Muller Counter. • Scintillation methods are especially employed for counting gamma radiations. • The method selected for the measurement of radioactivity depends upon the extent of energy & penetrability of radiation. 1. Ionisation chambers : • These are available in various shapes and sizes. • An ionisation chamber consists of chambers filled with gas & fitted with two electrodes kept at different electrical potentials & measuring device to indicate the flow of electric current. • Radiation brings about ionisation of gas molecules or ions which cause emission of electrons, which in turn reveals the changes in electrical current.
  • 19. 2. Proportional Couunters – • These are the modified ionisation chambers in which an applied potential ionisation of primary electrons causes thunderous bursting or production of more free electrons which get carried to the anode. • As for each primary electron liberated, much more additional electrons get liberated, the current pulse through the electrical circuit is amplified. • The voltage range over which the gas amplification (ionisation) occurs is called proportional region, the counters working in this region are called Proportional Counters. 3. Geiger – Muller Counters – • These are the still most population detectors. • They do not need use of a high gain amplifier and they can detect α, β, γ radiations. • G-M counter is having ionising gas & also having quenching vapour whose functions have been – 1. To prevent the spurious pulses that may be produced due to positive ions reaching the cathode. 2. To absorb the photons emitted by excited atoms & molecules returning to their ground state.
  • 20. • Both Chlorine & Bromine are generally employed as quenching agent. • Ethyl alcohol & ethyl formate are used as organic quenching agents. •
  • 21. Operation of Geiger – Muller Counters • A G-M probe unit is regarded as an electrical switch, in which each pulse may make to current to pass to scaler to counting unit for recording the number of pulses. • In order to operate the G-M counters, a source of high voltage, together with a low-gain amplifier & sealing unit of registering the pulses are needed. • When the voltage on the current gets raised, no registration of pulses will be observed until a certain voltage gets raised. • The counting rate increases rapidly to the threshold & at 150-200 V or more, the counting rates becomes sensibly constant. • At the same time size of individual pulses gets increased with voltage, so that at higher voltages there has been a tendency for spurious discharges to get initiated. • It has been one of the causes for slope of plateau.
  • 22.  Scintillation Counter • Alpha, beta, gamma can be detected by scintillation counters. • Ionizing radiation strikes certain substances like phosphurus. • A flash of light given out. Flash is collected by photomultiplier tube, produces electric impulses. • Impulse on amplification is recorded by scaler. • Counter consists of a scintillation crystal coupled with photomultiplier tube, an amplifier and scaler. • For gamma radiation, phosphurus in crystals sodium iodide activated with about 1% thalium. Enhances the degree of flurescence. • Γ radiation passing through a small window enter the crystal, produces small flash of light. • This is brought to photomultiplier tube, detects flash and amplifies it into an electrical impulse. Impulse recorded by scaler.
  • 23.  Radio Opaque contrast media • Radio opaque contrast media (ROCM) are diagnostic drugs used for the enhancement of radiographic (x-ray) examinations. Radio opaque substances are those compounds, both organic and inorganic, that have the property of casting a shadow on x- ray films. These substances has the ability to stop the passage of x- rays and hence appear opaque on the x-ray examination. Such compounds and their preparations are called as x-ray contrast media. • Inorganic compounds like barium sulphate and some bismuth compounds are useful as radio opaque contrast media for diagnostic use. These are administered either as orally or intravenously . These compounds are useful for examination of gastrointestinal tract, kidney, liver, gall bladder and bile duct, blood vessel of heart, etc.
  • 24.  Barium Sulphate Molecular formula: BaSO4 Molecular wt.: 233.43g/mol Properties: It is fine white, odourless, tasteless, bulky powder and free from grittiness. The salt is insoluble in water, organic solvent, dilute acids and alkalies. It is soluble in concentrated sulphuric acid. It can be solubalised with sulphuric acid or by fusing it with alkali carbbonates. Once it converted to carbonates, it reacts with acids easily. Preparation: Barium sulphate is obtained in commercial amounts from the mineral barite, after mining and processing. The processing of the impure barite involves heating it with coke (carbon) to form the water-soluble barium sulfide (BaS), which is then separated from the impurities and reacted with sulphuric acid to give the pure barium sulphate product : BaS + H2SO4 BaSO4 + H2S Another method to obtain pure barium sulphate is by reacting barium carbonate or barium chloride with sulphuric acid. BaCl2 + H2SO4 BaSO4 + HCl
  • 25.  Uses • Barium sulphate is widely used as a radio-opaque agent or x-ray contrast agent to diagnose gastrointestinal medical conditions. • It is administered by enema before x-ray examination in the form barium meal to make the intestine tract opaque to x-rays, so that it could be photographed. • Barium meal – it is suspension of barium sulphate. • Storage - It is stored in a well closed container.
  • 26. To learn something new, you need to try new things and not be afraid to be wrong – Roy T. Bennett