The Development and Use of Radioactive Isotopes as Medical Tracers

What Is A Medical Tracer:

In modern medicine the role of the radioactive isotope is incredibly versatile, and their use has
become much more common and accessible since their inception in 19111. Radioisotopes can be
effective tools in both diagnosis and therapy. Radioactive substances have to have very specific
properties in order to be used as medical tracers, firstly they must be gamma-emitting sources, as
gamma a from of radiation that will be able to penetrate the body and pass out of the patient and so
can be detected by medical imaging equipment4. It is also important that the radioisotope has a short
half-life so that the activity of the isotope is high and thus only a small amount of the tracer is
required in order for it to be an effective tracer4.

The Origin Of the Medical Tracer:

The idea came from George De Hevesy whilst he was working under Ernst Rutherford, he thought
that radioactive substances could be used as indicators1. The idea was first used to investigate the
solubility of lead salts alongside Austrian-born British chemist Friedrich Paneth, but De Hevesy
believed that the use of these radioactive isotopes could be used to observe and diagnose problems
in biological systems1. However at the time the only available naturally occurring radionuclides
were incredibly poisonous and so any live trials would be impossible to conduct1. However in order
to test his theory he conducted one experiment on a plant - a broad bean plant (Vicia Faba) - using
radioactive lead samples to observe the way lead was absorbed by the plant and subsequently
distributed1.

Artificial Radioactivity:

One of the biggest steps in the development of radiotracers for the diagnosis and treatment of
disease was the work done by Frédéric and Irène Joliot-Curie - French scientists and husband and
wife - to create radioactivity in chemical elements that weren’t naturally radioactive2. This is called
artificial radioactivity and the first radioactive isotope they produced was of phosphorus and was
produced as a result of the bombardment of aluminium with alpha particles2. This short-lived
isotopes emitted both beta particles ( high speed electrons) as well as giving off energy in the form
of electromagnetic radiation - ( gamma rays ), The isotope would then decay into a stable form of
silicon2. The married scientists also managed to produce radioactive isotopes of both nitrogen and
aluminium by using the same method of bombardment of boron and magnesium atoms.

How Artificial Radioactivity has been used:

When artificially radioactive isotopes are used to monitor chemical reactions or the function of
organs and organisms then they are referred to as radioactive tracers. One of the first human based
experiments to use a tracer was an investigation to show that iodine is taken up by the thyroid
gland, that sits at the bottom of the oesophagus, and was completed by Frédéric Joliot-Curie and
Antoine Lacassagne2. This is still used in todays medicine in order to check the thyroid gland is
functioning properly. A minute sample of radioactive iodine is given to someone who is suspected
of having a thyroid problem. If the gland is operating normally then the radioactive iodine would
pass through the gland and could be detected by an x-ray film, however if the gland is not
performing correctly then the radioactive iodine would not reach the thyroid gland and so would not
show up on the film and would indicate to the doctor that this organ is not performing it’s function
properly2. Iodine-131 was the radioactive tracer used to investigate the thyroid as it could be picked
by nuclear medical imaging equipment such as the gamma camera. This is because around 10% of
its radioactive energy is given as gamma rays and thus it can be detected3. However, 90% of the
radioactive energy given off from this unstable isotope is beta radiation which can cause damage to
the patients tissues as it is an ionising form of radiation and it offers no benefit as it cannot see the
isotope on the nuclear imaging equipment3. In light of this alternative isotopes of iodine have been
used, such as iodine-123 which is less damaging, however on occasion - particularly when the only
function of the tracer is for nuclear imaging - the iodine-131 isotope is used because it is
inexpensive compared to other isotopes, and studies have shown very small doses of it do not
contribute to an increase in the risk of thyroid cancer3.

The aforementioned radioactive phosphorus isotope can also be used as a medical tracer, as they are
often used to accurately ascertain the location, cause and severity of a cardiac arrest2. The
phosphorus is injected into the bloodstream of a patient who recently suffered a heart attack and
passes through the veins until it reaches the heart, where it will attach itself to any damage muscle
tissue within the heart2. These muscle tissues will show up on x-rays that allow the doctor or nurse
to determine the extent of the damage to the heart2.

Positron Emission Tomography:

Positron emission tomography (PET) is a medical imaging technique used to measure the metabolic
activity of body tissue cells. It is most commonly used to visualise the biochemical changes (e.g. the
metabolism of the heart muscle) taking place within the bodies of cancer patients, or patients who
suffer from a brain or heart conditions5. The scan works by using a radiopharmaceutical that emits
positrons as it decays , the positrons that are emitted then go on to react with electrons and
annihilate because the positron is the electrons corresponding antiparticle. In this process
(annihilation) the masses of both particles are converted into a high energy pair of photons4.

The most commonly used radiotracer in PET scans is fluorine-18, a radioactive isotope with a half
life of around 110 minutes. The fluorine-18 nucleus decays into an oxygen-18 nucleus, a positron, a
neutrino and a gamma photon4. Due to it’s relatively short half life fluorine-18 must either be made
on site or at a laboratory (that contains a particle accelerator) that is close to the hospital or
treatment centre4.

One method of producing fluorine-18 is to to send high speed protons to collide with an oxygen-18
nucleus to produce the fluorine-18 nucleus as well as neutrons4. This is a common method to use
due to the natural abundance of oxygen-18, as around 20% of the naturally occurring oxygen exists
as this isotope4.

Most PET scanners use a slightly modified medical tracer, called fluorodeoxyglucose (FDG)
because the human body treats it as normal glucose4. This means the tracer, once injected to the
patient accumulates in the tissues and muscles with a high rate of respiration. However the
modification is that the naturally occurring glucose has been tagged with a radioactive fluorine-18
atom in place of one of the oxygen atoms and the radioactivity from this fluorine-18 atom allows
the movement and function of the glucose to be monitored using gamma detectors.

An alternative to fluorodeoxyglucose is carbon monoxide (a toxic compound usually produced

when a substance undergoes incomplete combustion due to a lack of oxygen) made using a
carbon-11 radioactive isotope4. This isotope also emits a positron as it decays but has a shorter half-
life of around twenty minutes. The carbon monoxide molecule is extremely good at attaching on to
the haemoglobin molecule which exists in red blood cells and so the tracer can easily be transported
throughout the body and the concentrations of carbon monoxide is easily monitored with a PET
scan4.

Once the positron has undergone annihilation with an electron, two gamma ray photons of equal
energy are emitted at 180° to each other (in order to conserve momentum), and it is these emitted
photons that allow us to build up an image. The patient is laid on a table encompassed by a ring of
gamma detectors. Each of the individual detectors contains a photomultiplier tube and a scintillator
and each time one detects a gamma photon at it’s scintillator then a pulse is generated and sent to a
high speed computer which is connected to all of the gamma detectors4.

The PET scanner detects the pairs of gamma photons produced by the annihilation and then the
computer can determine, using the difference in arrival times of the two photons at the diametrically
opposed detectors, the point of annihilation. This is possible because the photons travel at the same
speed - the speed of light (c) ≈ 3⨉108 ms-1 - and we know that on average a positron will travel
about 1mm from its original emission point before it annihilates with an electron.4 The signals
produced from each of the detectors is fed into the computer which analyse and combine the
information to generate an image which can be displayed on a screen. This image shows the areas
of the body which contain different concentrations of the radiopharmaceutical by using different
colours and brightnesses4.

Costs and Benefits of PET Scans:

The PET scan is non-invasive (meaning that no surgery is required) which decreases the overall risk
to the patient as there is no possibility of infection or complications with surgery. It is also possible
for a PET scan to be used in conjunction with another nuclear imaging technique such as a
computer tomography scan or magnetic resonance imaging- allowing more accurate diagnosis as
well as more detailed visualisations5. For example a PET/CT can also be used in the diagnosis and
treatment of lung cancer alongside providing more information on epilepsy, Alzheimer’s and
coronary artery disease5.

However PET scans can be extremely expensive because of the requirement for specialised
laboratories to be on site or very close due to the short half-lives of the isotopes used4. In general
PET scanners can only be found in larger hospitals and they would only be recommended for
patients whose treatment plans are very complex or involve the treatment of various diseases and
problems simultaneously4.
References:
1. https://www.tandfonline.com/doi/pdf/10.3109/02841869509127236
Sten Carlson (1995) A Glance At The History Of Nuclear Medicine, Acta Oncologica, 34:8,
1095-1102, DOI: 10.3109/02841869509127236

2. STACEY R. MURRAY (2019) “The Development of Artificial Radioactivity." Science and Its
Times: Understanding the Social Significance of Scientific Discovery.
Date Last Accessed : 05/04/2019 .
https://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/development-
artificial-radioactivity

3. Wikipedia (2019), Iodine-131. [Online],

Date Last accessed: 06/04/2019
https://en.wikipedia.org/wiki/Iodine-131

4. Graham Bone, Gurinder Chadha (ed.), Nigel Saunders (2015), A Level Physics for OCR, Oxford,
Oxford University Press 


5.John Hopkins Medicine (2019), Positron Emission Tomography (PET). [Online],

Date last accessed: 06/04/2019
https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/positron-emission-
tomography-pet