Radiopharmacy I
Nuclear medicine
Pharmaceutics II
Year 3
Baxter Kachingwe (PhD)
Objectives
• Understand three principal types of radioactive decay (i.e., alpha,
beta, gamma)
• Examples of alpha-emitters, beta−- and beta+-emitters, electron
capture and isomeric transitions
• Describe types of radionuclides and principles of their medical use
and delivery method(s)
• Radionuclide production of beta+-emitters
• Generating and preparation of radiopharmaceuticals (e.g. 99mTc
based radiopharmaceuticals)
• Identify indications for use of nonradioactive pharmaceutical in
nuclear medicine
Introduction
Elements that emit radiation are known as radionuclides
• Applications in medicine
Radionuclides
• Radioactive half-life
• Time required for a radionuclide to decay to 50% of its original activity
Introduction
Is a radioactive pharmaceutical agent that is used for diagnostic
or therapeutic procedures
• Consists of:
• Radioactive element such as 133Xe,
• Simple salt such as 131I-NaI, or
• Labelled compound (drug and a radioactive component) e.g.131I-
iodinated proteins and 99mTc-labeled compounds
Radiopharmaceuticals
Have two main applications
• Diagnosis of disease - well established - two types:
• Used in tracer techniques for measuring physiological parameters
• (e.g. 51Cr-EDTA for measuring glomerular filtration rate)
• Used in diagnostic imaging
• (e.g. 99mTc-methylene diphosphonate (MDP) used in bone scanning).
• Treatment of disease - evolving
• Mainly administered through IV route
Radiopharmaceuticals
Goal
• Cause minimal or tolerable damage to healthy, adjacent tissue
• Optimum dose
• Desired outcome with least amount of radiation dose or exposure to
patient
• Difficult to achieve -their characteristics
• Clinical utility determined mainly by the radionuclide's physical
properties (e.g. radiation, energy, half-life)
• Agent safe for human use must satisfy
• Medicines regulatory authority (PMPB/PMRA)
• Nuclear regulatory authority (AERA Malawi)
Nuclear medicine
• Medical specialty radiopharmaceuticals to assess bodily
functions and to diagnose and treat disease
• Specially designed cameras allow doctors to track the path of
these radioactive tracers
• Single Photon Emission Computed Tomography (SPECT)
• Positron Emission Tomography (PET)
Nuclear pharmacy (Radiopharmacy)
Specialization discipline
• Concerned with manufacture or preparation of radioactive
radiopharmaceuticals
Comprises a rational understanding of radiopharmaceuticals:
• Pharmaceutical, chemical, physical, biochemical, biological
• Design, preparation and quality control
• Relationship with clinical application
• Management, selection, storage, dispensing, and proper (safe and effective) use
Examples of application
• Cardiology (e.g., myocardial perfusion)
• Oncology (e.g., tumor imaging and localization)
• Neurology (e.g., cerebral perfusion)
• Infection imaging (Diagnostically)
• Nephrology (Diagnostically
• Thyroid cancer, graves disease, hyperthyroidism, and bone pain
palliation associated with skeletal metastasis (Therapeutically)
• Pheochromocytoma and neuroblastoma (Therapeutically)
• E.g. 131I or 123I-labeled MIBG [m-iodobenzylguani-dine]) and radiolabeled
somatostatin analogs
Radioactivity
Radioactivity
Radioactivity
• Decay equation (e−λt)
• Activity of a radioactive material is expressed as the number of
nuclear transformations per unit of time
• Radioactivity decreases with time
• Fraction of nuclei disintegrating with time is always constant
Radioactivity
• Half-life is inversely proportional to decay constant
• Where λ is decay constant which is unique for each nuclide
• Radioactive half-life
• Time required for a radionuclide to decay to 50% of its original activity
Radioactivity
• Fundamental unit of radioactivity is curie (Ci), defined as 3.700
× 1010 nuclear transformations per second or disintegrations per
second (dps)
• Radiopharmaceutical doses are dispensed to patients in units of
activity, typically mCi or μCi.
Radioactivity
Radioactivity
Three main types of radiation decay are:
• Alpha particles
• Beta particles
• Gamma photons (or gamma rays)
Radioactivity
Alpha particles
• Largest mass and charge of radiation
• Consists of two protons and two neutrons
• Loses energy loss velocity decreases
• Attracts electrons and becomes a helium atom
• Unable to pierce outer layers of skin or penetrate a thin piece of
paper
• Charge is large cause great deal of damage to immediate
area by breaking down DNA
Radioactivity
Beta particles
• Either electrons with negative charge, negatrons (β−), or
positive electrons, positrons (β+)
• Range of more than 100 feet in air and up to about 1 mm in
tissue
• Not destructive
• Can be used therapeutically
• Possesses a lot of kinetic energy, thousands to millions of
electron volts
Radioactivity
Gamma photons (or gamma rays)
• Electromagnetic vibrations shorter wavelength than light
• High energy
• Very penetrating
Radionuclides used in nuclear medicine
Alpha-emitters
• Alpha-decay
• Emits helium nucleus, or alpha-particle
• Commonly occurs with heavy nuclei
Beta-emitters
• Beta-decay
• Emission of -vely charged beta−-particle (electron)
• Emission of +vely charged beta+-particle (positron)
Radionuclides used in nuclear medicine
Electron capture
• Proton rich nuclei capture electrons from atom’s electron orbital
• Results in transformation of a proton to a neutron within nucleus
• Subsequent rearrangement of electrons orbiting nucleus results
in emission of X-rays or gamma-rays
• Useful in diagnostic imaging
Isomeric transition
• Some radionuclides exist for measurable periods in excited, or
isomeric states prior to reaching ground
• This form of decay involves emission of a gamma-ray
Radionuclides used in nuclear medicine
Radionuclides used in nuclear medicine
Some radiopharmaceuticals frequently
used in daily practice
Production of radionuclides
• Nuclear reactor
• Cyclotron
• Generator (Mo99)
Imaging procedures
• Dynamic
• Rate of accumulation and removal of radiopharmaceutical from a
specific organ
• Static
• Perfusion and morphologic information, such as assessing adequacy
of blood flow; organ size, shape, and position; and any space-
occupying lesions
Principles of 99mTc-radiopharmaceutical
production
Physical and chemical properties of 99mTc make it nearly ideal
for imaging purposes
• A 6-h half-life (T1/2)
• Long enough to allow imaging to take place in working day
• Short enough - patients not radioactive for long periods (in 24 h, or 4
half-live, radioactivity decayed by 94%)
• Emits gamma-rays of 140 keV energy - ideal for modern
gamma-camera
• No particulate emissions that, if present, would add to patient’s
radiation dose
Principles of 99mTc-radiopharmaceutical
production
Physical and chemical properties of 99mTc make it nearly ideal
for imaging purposes
• A 99Mo/99mTc – generator - readily available in sterile and
pyrogen-free form
• Versatile coordination chemistry and will allow large number of
ligands to complex with it
• Wide range of radiopharmaceuticals for investigations
Production of 99mTc
Mechanisms of radiopharmaceutical localization
Positron emission tomography (PET)
Positron emission tomography (PET)
• Noninvasive modality for diagnosis and management of cancer
• PET yields high-quality images that characterize substrate
metabolism, cellular proliferation, receptor density, and other
parameters used to identify cancer and evaluate its response
to treatment
Application of Positron emission
tomography (PET)
• Mapping 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
Application of Positron emission
tomography (PET)
• Detect functional abnormalities before anatomic changes have
occurred
• In tissues such as brain, heart, cancer (breast and colon)
• Epilepsy
• [18F]-fluorodeoxyglucose - evaluating tumours
Positron-emitting radiopharmaceuticals used
in common PET imaging procedures
Positron-emitting radiopharmaceuticals used
in common PET imaging procedures
Properties of radiopharmaceuticals used
in common PET imaging procedures
Therapeutic uses of radiopharmaceuticals
Designed to deliver
• Therapeutic doses of ionizing radiation to specific disease sites
(cancerous tumors) with high specificity
Design optimizes
• Balance between specific targeting of disease (cancer) and
clearance of radioactivity from non target radiosensitive tissues
• Also necessary to consider physical radioactive decay
properties of radionuclide
Therapeutic uses of radiopharmaceuticals
• Sodium phosphate (32P)
• Polycythemia vera
• Chromic phosphate, (32P) and 89Sr-chloride
• Peritoneal effusions
• Radioiodine therapy
• Hyperthyroidism (Graves disease, Toxic multinodular goiter)
• Eradication of metastatic disease (thyroid cancer)
• Radioimmunotherapy (RIT)
• Uses antigen-specific monoclonal antibodies (MABs) or their derived
reagents to deliver therapeutic radionuclides to tumorous tissue
Therapeutic uses of radiopharmaceuticals
Radionuclide therapy targeting
• Ions (MW 102)
• Low molecular weight drugs (MW 102–3)
• Peptides (MW 103)
• Radiolabelled antibody fragments
Therapeutic uses of radiopharmaceuticals
Radionuclide therapy targeting
• Various proteins (MW 104)
• Intact antibodies (MW 105)
• Chase molecules (avidin)
• Metabolisable linkers
• Local delivery
• Antibody-directed enzyme prodrugs
• Liposomes (MW 106)
Recommended antidotes for internal
contamination with selected radiation
Drug antidotes for radiation
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Acetazolamide
• Diuretic - used to treat glaucoma
• Increase cerebral blood flow 23% ± 8% in normal vessels
• Used in cerebral perfusion studies
• Differentiate normal from abnormal blood vessels
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Captopril
• Diagnosis of renovascular hypertension in hypertensive patients with
abdominal bruits, declining renal function, and poorly controlled
hypertension with drug therapy
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Cimetidine
• Meckel diverticulum
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Dipyridamole and adenosine
• Alternative to treadmill stress test prior to cardiac imaging
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Furosemide
• Confirm or rule out mechanical renal obstruction during renal
scintigraphy when significant retention of radioactivity is noted in renal
pelvis
Interventional pharmaceutical drugs used
to complement radiopharmaceutical
• Vitamin B12
• Schilling test determines patient's capability to absorb radioactive
vitamin B12 from intestine
Concurrent administered drugs known to
interfere with tumor and abscess localization
Scintigraphy
Drugs known to interfere with brain Drugs known to interfere with renal
imaging imaging
Concurrent drugs known to interfere with
myocardial perfusion scintigraphy
Thank You.
