RADIOPHARMACEUTICALS

Radiopharmaceuticals:
• pharmaceutical formulations consisting of radioactive
substances (radioisotopes and molecules labelled with
radioisotopes), which are intended for use either in diagnosis
or therapy.
• The use of radioactive material necessitates careful and safe
handling of these products by trained and authorized
personnel, in approved/authorized laboratory facility
Units of Radioactivity:
• Becquerel (Bq) - the International System (SI) unit of
radioactivity in one nuclear transmutation per second;
named after the scientist Henri Becquerel.
• Curie (Ci) - The old unit of radioactivity; named after the
scientists Madame Marie Curie and Pierre Curie, the
pioneers who studied the phenomenon of radioactivity.
• One Ci is the number of disintegrations emanating from 1 g
of Radium-226, and is equal to 3.7 x 1010 Bq.
Becquerel (Bq)
• One becquerel is defined as the activity of a quantity of radioactive
material in which one nucleus decays per second.
• This is a very small unit, and multiples are often used:
• 1 MBq = 1 mega Becquerel = 1,000,000 Bq
• 1 GBq = 1 giga Becquerel = 1,000,000,000 Bq
• 1 TBq = 1 tera Becquerel = 1,000,000,000,000 Bq
• The radioactivity of an environment, a material or a foodstuff is given
in Becquerel’s per kilogram or per liter.
Gray (Gy)
• defined as the measurement of the amount of radiation your cells
absorb or the absorbed dose of radiation per unit mass of tissue.
• One gray is the absorption of one joule of radiation energy per
kilogram of matter.
• 1 Gy = 1 joule per kilogram
• Sub-multiples are often used:
• 1 mGy = 1 milligray = 0.001 Gy
• 1 μGy = 1 microgray = 0.000001 Gy
• 1 nGy = 1 nanogray = 0.000000001 Gy
Sievert (Sv)
• a measure of the health effects of low levels of ionizing radiation on
the human body.
• At equal doses, the effects of radioactivity on living tissue depends on
the type of radiation (alpha, beta, gamma, etc.), on the organ
concerned and also on the length of exposure.
• Contrary to the Becquerel, the sievert is a very large unit
• use sub-multiples:
• 1 mSv = 1 millisievert = 0.001 Sv
• 1 μSv = 1 microsievert = 0.000001 Sv
Half-Life (T1/2).
• The time in which a given quantity of a radionuclide
decays to half its initial value
• The rate of decay of radioactive substances
Half-Life Period:
• The time in which a given quantity of a radionuclide decays to half its
initial value is termed as half-life (T1/2).
Properties of α, β, γ radiations:
• All substances are made of atoms.
• These have electrons (e) around the outside, and a nucleus
in the middle.
• The nucleus consists of protons (p) and neutrons (n), and is
extremely small.
• (Atoms are almost entirely made of empty space!).
• Negatron - Emitted when neutrons exceed protons beyond a
stable ratio that occurs mainly in the elements of atomic
numbers above 63
Nuclear Decay
• In some types of atom, the nucleus is unstable, and will
decay into a more stable atom.
• This radioactive decay is completely spontaneous.
• When an unstable nucleus decays, it may give out:
• an alpha particle (α)
• a beta particle (β)
• a gamma ray (γ)
Alpha particles
• Alpha particle radiation consists of two neutrons and two
protons, as they are charged they are affected by both
electric and magnetic fields.
• The speed of the alpha-particle depends very much on the
source, but typically are about 10% of the speed of light.
Alpha particles
• The capacity of the alpha-particle to penetrate materials is
not very great
• usually penetrates no more than a few centimeters in air and
is absorbed by a relatively small thickness of paper or human
skin.
• However, because of their speed and size, they are capable
of ionising a large number of atoms over a very short range
of penetration.
Alpha particles
• This makes them relatively harmless for most sources that
are about a meter or more away, as the radiation is easily
absorbed by the air.
• But if the radiation sources are close to sensitive organs
alpha-particle radiation is extremely dangerous
Beta particles
• Beta-particle radiation consists of fast moving electrons.
• Every beta-particle carries either one negative or one
positive electronic charge (±1.6 × 10-19 coulomb: -e, +e).
• They are affected by electric and magnetic fields.
• The speed depends on the source, but it can be up to 90% of
the speed of light.
Beta particles
• Beta-particles can penetrate up to 1 m of air.
• They are stopped by a few millimeters of aluminum or
Perspex® (acrylic sheet).
• Their ionizing capacity is much less than that of alpha-
radiation.
• They are very dangerous if ingested.
Gamma rays
• Gamma radiation does not consist of charged particles, it is a
form of very short wavelength electromagnetic energy.
• They travel at the speed of light (3 × 108 m/s).
• Gamma radiation is very difficult to stop, it takes up to
30mm of lead.
• Lead containers- used to safely store and transport
radioisotopes
Gamma rays
• Although the ionising capacity of gamma radiation is
considerably smaller than that of beta-radiation, their high
penetration power means that they are dangerous even at a
distance.
• They can penetrate our bodies and hit sensitive organs.
• Gamma ray emissions is preferrable in diagnostic
radiopharmaceuticals
• They are particularly dangerous if ingested or inhaled.
Measurement of Radioactivity
1. Gas-filled tube counters e.g. the Geiger Muller
Counter
2. Scintillation Counters
3. Semi-conductor Detectors
The Geiger Counter:
• a handheld device used for the
detection of ionizing radiation by
laboratory safety personnel
• Any atoms of gas struck by the γ-
rays entering the tube are
ionized, causing a discharge.
• Discharges are monitored and
counted by electronic circuitry
and the output is reported as
counts/sec or Rontgens/hr or
mR/hr.
Scintillation Counters:
• Preferred for measuring alpha-
particles
• Crystals of certain substances e.g.
cesium fluoride, cadmium
tungstate, anthracine and sodium
iodide emit small flashes of light
when bombarded by γ-rays.
• The most commonly used
phosphor in scintillation counters is
NaI with a minute quantity of
thallium added.
Scintillation Counters:
• In the instrument, the crystal is positioned against a
photocell which in turn is linked to a recording unit.
• The number of flashes produced per unit time is
proportional to the intensity of radiation.
Semi-Conductor Detectors:
• A semi-conductor is a substance whose electrical conductivity is
between that of a metal and an insulator.
• It is noted that Ge(Li) Germanium-Lithium semi-conductors are
excellent detectors of γ-rays with a resolution ten times higher than
NaI (Th) scintillometers.
• The main disadvantage of these is a lower efficiency for higher energy
x-rays.
• Besides, Ge(Li) semiconductors need to be cooled by liquid nitrogen
and are hence cumbersome and not suitable as field instruments
X-ray scan
• X-rays - a type of radiation that can pass through most objects,
• X-ray scan - Common imaging test that uses electromagnetic
radiation to create pictures of the inside of the body
• radiopaque contrast media - chemical compounds containing
elements of high atomic numbers which will stop the passage of x-
rays (often iodine-based)
• Diatrizoate: Used to diagnose urinary tract diseases
• Iophendylate: Used to locate spinal tumors
• Iodixanol: Used during coronary angiography, especially in patients with renal
dysfunction
• Iohexol: Used in myelography and computerized tomography
CT Scan
• Computed tomography aka CAT scan
• based on portrayal of the distribution
of attenuation of x-rays passing
through the body
• The X-ray beam moves in a circle
around your body, taking many
different views of the same organ or
structure.
POSITRON EMISSION TOMOGRAPHY
• Aka PET scan - the primary imaging technique used with
radiopharmaceuticals in nuclear medicine
• employed to study cerebral physiology and a noninvasive modality for
the diagnosis and management of cancer
• Radiolabeled tracers - natural biochemicals labeled with
radionuclides of carbon, nitrogen, oxygen, and fluorine.
• injected in nonpharmacologic doses are used to construct three-dimensional
images by computer
• Example: Fluorine-18 FDG for evaluation of glucose metabolism of the brain
POSITRON EMISSION TOMOGRAPHY
• Uses for imaging of:
• regional blood flow
• oxygen metabolism
• regional blood volume
• rates of use of metabolic substrates
• receptor-specific tracer binding
• bone remodeling
• tumor receptor density
• reporter gene expression
POSITRON EMISSION TOMOGRAPHY
• INDICATIONS:
• Lymphoma - assess estrogen receptors in primary and metastatic
breast cancers, and to identify resectable colorectal tumor
recurrence.
• Epilepsy - clinical assessment of symptoms and signs to try to localize
areas of the brain that are the foci of epileptic seizures when surgical
intervention is the only remaining method to prevent the seizures.
SPECT scan
• Single Photon Emission
Computed Tomography
• nuclear imaging test that uses a
radioactive tracer (primary Tc99
compounds) and special cameras
to create 3D images of the inside
of your body
MRI
• Magnetic resonance imaging
• uses radio waves and strong magnets to create detailed pictures of
the inside of the body
• exploits the variation in regional concentrations of hydrogen and
nuclear relaxation parameters to generate image contrast
• provide information about free water content, relative blood flow,
and the concentration of contrast agents
CONCURRENT ADMINISTERED DRUGS KNOWN TO
INTERFERE WITH RADIOPHARMACEUTICAL
IMAGING
• ANTITHYROID – methimazole, propylthiouracil
• ANTIEPYLEPTICS/ANXIOLYTICS – phenytoin, lorazepam, phenobarbital
• ANALGESICS – acetaminophen, ibuprofen
• ANTICOAGULANTS/ANTITHROMBOTICS – heparin, warfarin
• ANTIBIOTICS - cotrimoxazole, penicillin G, ampicillin
• CARDIAC DRUGS - Beta-blockers, calcium-channel blockers, digoxin,
propranolol
• BRONCHODILATING AGENTS
Pharmaceutical Application Of Radioactive
Substances
• Treatment of Cancers and Tumours
• Americium 241 used as antineoplastic.
• Californium 252 used as antineoplastic.
• Cobalt 60 used as antineoplastic.
• Gold 94 used as antineoplasatic.
• Holmium 66 being developed for diagnosis and treatment of liver
tumours.
• Iodine-125 used in cancer brachytherapy (prostate and brain).
Pharmaceutical Application Of Radioactive
Substances
• Treatment of Thyroid Disease with Iodine 131
• Radioactive isotopes of iodine have wide use in diagnosis
and therapy
• Iodine-131 is therapeutically used for to treat the following:
• Thyroid cancer
• Hyperthyroidism (including Graves’ disease, toxic multinodular
goiter, and toxic autonomously functioning thyroid nodules)
• Nontoxic multinodular goiter.
Pharmaceutical Application Of Radioactive
Substances
• Note: Lugol’s solution is given to patients at least 24 hours before the
administration of radioactive iodine to saturate the thyroid gland with
iodine and to prevent the uptake of radioactivity.
• Iodism - Irritative phenomenon to the skin and mucus membrane
exhibited by rashes and headaches when excessive amount of Iodine
is administered
Pharmaceutical Application Of Radioactive
Substances
• Palliative Treatment of Bone Metastasis:
• Various radioisotopes and pharmaceuticals are used to deliver
palliative treatment of bone metastases, including:
• samarium-153 (Sm-153)
• strontium-89 (Sr-89) chloride - Diagnostic to scan bones
• phosphorus-32 (P-32) sodium phosphate.
• The two most common side effects occurring from
radiopharmaceutical therapy for metastatic bone disease are initial
increased bone pain (flare) and a decrease in WBC and platelet
counts.
Pharmaceutical Application Of Radioactive
Substances
• Treatment of Arthritis
• Erbium-169: Use for relieving arthritis pain in synovial joints
• Diagnostic Radiopharmaceuticals:
• Ammonia N 13 Injection used for diagnostic coronary artery disease.
• Chromium 51 used for diagnosis of pernicious anaemia.
• Holmium 166 used for diagnosis and treatment of liver tumours.
• Iodine 125 used diagnostically to evaluate the filtration rate of
kidneys
Review notes
Technetium 99m compounds – most commonly used for diagnostic and therapeutic
1. Liver

• Tc99m IDA (Imino diacetic acid) – hepato-biliary studies

• Tc99m phytate – liver imaging → for potency studies (“liver phytes potent toxins”)
• Au198 – liver scanning
• I131 Rose Bengal – tracer of liver function
• Na iodohippurate – diagnosis of liver functions
2. Kidney

• Tc99m heptagluconate -kidney imaging → renal function determination

• Hg197 chlormerodrin – kidney and brain scintillation scanning
Review notes
1. Heart
• Tc99m sestamibi/ methoxy isobutyl isonitrile – myocardial perfusion agent
• I131 NaI – cardiac output determination → blood plasma volume
2. Thyroid
• Tc99m pertechnetate – thyroid scanning
• I125 NaI – determination of thyroid function
Review notes
1. Others
• Tc99m etidronate/ phosphonates - Best radiopharmaceutical agent for bone
imaging
• Tc99m macroaggregate albumin – lung scanning
• Tc 99m-exametazine - used as adjunct in the detection of altered regional
cerebral perfusion in stroke.
• Cr51 – spleen imaging, RBC mass
• P32 Na Phosphate – treatment of polycythemia vera
• Co57 cyanocobalamin – diagnosis of pernicious anemia
• Se75 selenomethionine – diagnosis of pancreatic tumors
Review notes
• Radon - recovered from the radioactive decay of radium
• Astatine - A synthetic radioactive, metallic halogen that resembles
iodine but is more metallic
• Xe-133 - prolonged retention in the lungs can cause Obstructive lung
disease
• Chromatography testing of technetium radiopharmaceuticals - check
for Radiochemical purity
Storage of Radioactive Substances
• should be kept in well-closed containers and stored in an
area assigned for the purpose.
• should be such that the maximum radiation dose rate to
which persons may be exposed is reduced to an acceptable
level.
• Care should be taken to comply with national regulations for
protection against ionizing radiation
Storage of Radioactive Substances
• preparations that are intended for parenteral use should be
kept in a glass vial, ampoule or syringe that is sufficiently
transparent to permit the visual inspection of the contents.
• Glass containers may darken under the effect of radiation