Radiopharmacy 1

(PHAR2013)

Dr Georgina Marsh
 Lecture Overview
• Nuclear chemistry revision
• Radioactive decay
• Nuclear medicine
• Radiopharmaceuticals
– Treatment
– Diagnosis
• Production and dispensing of radionuclides
radiopharmaceuticals
 Structure of Atomic Nucleus
• Nuclear configuration conventionally written as:
99 m
X*
Mass number A
Atomic number Z
e.g. 43 Tc
• Where * is reserved for an indication of the
existence of a metastable (isomeric) state sufficiently
long lived to allow it to be investigated
independently of its ground state

99 m
43Tc may be written as Tc-99m
Stability of the Atomic Nucleus
Proton Neutron
 Radioactive Decay
• Nuclear stability needs a balance between protons
and neutrons
• Radioactivity: spontaneous transformation of an
unstable nucleus to a more stable nucleus
• Releases ionising radiation “Radioactivity is
–  particles measured in becquerel
–  particles (Bq) or curie (Ci)”
–  rays (electromagnetic radiation)
• Elements that emit radiation are called radionuclides
 Radioactive Decay
1. Emission of an alpha () particle
Alpha particles are essentially Helium nuclei.
Emission occurs spontaneously during the decay
of heavy elements, e.g. Radium-226

226 222 4 2+
88 Ra 86 Rn +  2
 Radioactive Decay

210
84 Po
www.bbc.co.uk (Associated Press)
 Radioactive Decay
2. Emission of beta (-) particle
Emission of beta (-) particle (an electron)
occurs in the presence of excess neutrons. The
atomic number z increases as neutrons are
converted to protons, e.g. phosphorus-32

32 32
15 P 16 S + -
 Radioactive Decay
3. Emission of positron (+) particle
Emission of beta (+) particle (a positron) occurs
in the presence of a deficiency of neutrons. The
atomic number z decreases as protons are
converted to neutrons, e.g. sodium-22

22 22
11 Na 10 Ne + +

…the positron quickly reacts with an electron resulting in annihilation

of both particles → two gamma rays travelling in opposite directions
 Radioactive Decay
4. Emission of gamma () radiation
Gamma radiation can accompany alpha or beta
emission. It can also occur during electron
capture (EC) or isomeric transition (IT), e.g.
technetium-99m

26 26
+Al
13 e -
12 Mg + 
What is Nuclear Medicine?

www.nucmedicine.com/images/Radiopharmaceuticals-1.pdf
 Nuclear Medicine
• Uses small amounts of radioactive substances (or
tracers) for the diagnosis or treatment of disease

• These tracers are injected, inhaled or swallowed after

which they travel to the organ or tissue being
investigated
 Nuclear Medicine
• Radiopharmacy is concerned with the manufacture
of radioactive medicines (radiopharmaceuticals)
• Used for:
• Diagnosis
– An aid used in the diagnosis of a disease (diagnostic
radiopharmaceuticals)
• Treatment
– In the treatment of a disease / condition (therapeutic
radiopharmaceuticals)
Treatment of Disease
 Radiotherapy
• Treatment of cancer
• Other conditions
• Ionising radiation used to attack malignant cells
• Three main types:
– External beam radiotherapy
– Sealed source radiotherapy
– Unsealed source radiotherapy
• External beam radiotherapy is the most common
 Radiotherapy
• External beam radiotherapy
• Angular approach is used to try and protect healthy
tissue

Tumour

Normal tissue
 Radiotherapy
• Sealed source radiotherapy
• Source of ionising radiation is located next to (or
inside) the required site
– Prostate cancer
– Cervical cancer
– Ovarian cancer…
• Typical radionuclides:
– Strontium-90
– Caesium - 137
 Radiotherapy
• Unsealed source radiotherapy
• Radionuclides administered to the patient
• Selectively taken up by specific
organs / tissue
– Thyroid
– Bone marrow…
• I131 emits beta radiation which
damages the thyroid
• But Gamma radiation also
emitted
Diagnosis of Disease
 Diagnostic Radiopharmaceuticals
• Medicinal products which include a radionuclide in
their composition that are used to facilitate the
diagnosis of a disease
– Tracer techniques for measuring physiological
parameters
– Diagnostic imaging
• Gamma emitters (less interaction with tissue)
 Tracer Techniques
Intravenous Cr-51
labeled EDTA can be
used to measure GFR
Blood samples taken
and radioactivity
measured

Glomerular filtration rate

(GFR): “The volume of
fluid filtered from the
renal glomerular
capillaries into the
Bowman's capsule per
unit time”

Level of Cr-51 EDTA in the blood falls…

Radionuclide Production & Dispensing
Radionuclides used in Nuclear Medicine
Radionuclide Physical half-life  energy
(keV)
Tc-99m 6 h 141
In-111 2.8 days 171 & 245
I-123 13 h 159
I-131 8.0 days 365
Tl-201 3.0 days 80
Gases
Kr-81m 13 s190
Xe-133 5.3 days 81
 Production of Radionuclides
• Radionuclides with long half-lives can be
manufactured at one site and transported to a
hospital
• Early nuclear medicine used radionuclides with longer
half-lives
• Iodine-131 (half-life = 8 days)
• What is the problem with a long half-life?
• Solution: use shorter half-life radionuclides (e.g. Tc-
99m, half-life = 6 hours)
• Radionuclide generator
 Radionuclide Generators
• Short-lived radionuclides can be produced in situ
– Molybdenum / technetium “Mo-tec” generator
• Generator manufactured  delivered to pharmacy
• Radionuclide removed (eluted or ‘milked’) from the
generator
• Radiopharmaceutical ‘prepared’ or dispensed
• Administered to
patient  imaging
Technetium Generator Design
Needle
Metal closure

Eluent Glass column

Lead shielding

Eluate

Sterile filter
 Mo-99 / Tc-99m Generator
• The generator would usually be eluted once daily
• Sodium pertechnetate (Na99TcO4) injection may be
used directly (possibly after dilution)
• Sodium pertechnetate may be transformed into a
different radiopharmaceutical
• Kits are available to simplify this latter process
– Sterile ingredients (all pre-packed)
– Freeze-dried
– Enclosed in nitrogen-filled vial

“Just add sodium pertechnetate solution”

 Mo-99 / Tc-99m Generator
• The reactions:

In generator
99 99 m
42 Mo 43 Tc +  -
+

In patient 99 99
Tc + 
m
43 Tc 43
140keV

This gamma emission is used in nuclear medicine

 Tc-99m – the ideal radionuclide?
• Half-life is 6 hours
– Long enough to allow imaging
– Patient does not remain radioactive for too long
• Gamma rays emitted by Tc-99m are the ideal energy
for modern gamma cameras
• No particulate emissions (e.g. alpha particles)
• Easily prepared using a generator
• Coordination chemistry of Tc-99m allows
complexation with a large number of ligands
 Summary
• Atomic nuclei can be unstable  radioactive decay
• Radionuclides can be used in (nuclear) medicine for
treatment and diagnosis
• Generators delivered to hospitals are used to
produce most radionuclides used in medicine