Radiopharmaceuticals Flashcards
X-rays give a good image of anatomy but a poor image of that?
Function.
Nuclear medicine scans give a good image of function but a poor image of what?
Anatomy.
What is a gamma camera?
This is the piece of technology used to image the radiation given off by the radioisotopes used in nuclear medicine imaging.
The philosophy of radiation protection follows which two basic tenants?
• All exposures shall be justified.
o The benefit gained outweighs the risk involved.
• All exposures shall be kept as low as reasonably practicable (ALARP).
We are constantly being exposed to radiation. Give some sources.
Radiation comes from cosmic radiation, radon gas coming from the ground, buildings, and foodstuffs to name a few.
What is a Sievert (Sv)?
This is the unit used to measure radiation energy in the tissue. Sievert is the unit quoted when looking at rules governing exposure.
What is the average radiation exposure for a member of the public in Sievert?
The average exposure for a member of the general public in the UK is 2.5 mSv per year.
In practice, what is the range of energy used, measured in sievert?
In practice, the levels of energy used, measured in Sievert, are often in the range of milliSievert (mSv) or microSievert (µSv).
How can sievert be calculated?
Sievert can be calculated by multiplying Gray by the quality factor (QF). For beta and gamma emitters, the quality factor is one.
Define the unit Gray (Gy).
This is the S.I. unit of absorbed radiation dose. It is one joule of energy absorbed per kg tissue.
Define the unit Bequerel.
This is the rate of degradation of radioisotopes (1 nucleus d.p.s). This unit or radiation measure says nothing about the radiation dose that patients or workers are exposed to, however.
In the US the equivalent of the Becquerel (Bq) is the Curie, what is one millicurie equivalent to?
In the US this unit is the Curie, with one millicurie being equivalent to 37MBq.
What is the main concern with radiation exposure?
The main concern with radiation exposure is carcinogenesis (formation of cancerous tumours).
What is the general rule of thumb when it comes to the effects of radiation exposure?
The general rule of thumb is that one should assume a risk, whatever the dose of radiation may be.
What is the risk of having serious side effects from exposure to a radiation dose of 2mSv?
1 in 15,000.
How can radiation exposure be limited?
- Increasing the distance between the radioisotope and the operator.
- Reducing the length of time that the operator/patient is exposed to radiation.
- Using shielding (usually lead).
In an effort to reduce radiation exposure, what must SOPs include?
- Staff training.
- Monitoring.
- Feedback (usually monthly).
Describe alpha particles.
These are He nuclei, with a charge of +2. They are comparatively large so collide with tissue, giving up their energy, and cause ion pairs. This leads to considerable damage in a small area.
Their range through tissue is a few mm. They can be easily shielded as they are ‘big’ molecules.
These particles have no use as diagnostic agents however they can be used as therapeutic agents (e.g. Ra-223).
What two types of beta particles are there?
Negative and positive beta particles.
Describe negative beta particles.
These are smaller than alpha particles so have less interactions with tissues (50 ion pairs per cm). Because they are smaller, they also have a greater range of penetration in tissues; this range can be up to several cm depending on energy max and energy mean.
These particles are also not used for diagnosis but are valuable for therapy.
Describe positive beta particles.
These are also known as positrons or antimatter. Immediately after emission from a nucleus, they collide with a negative beta particle. This leads to an annihilation reaction where matter is converted into energy (2 gamma particles/waves are formed).
Describe gamma rays.
Gamma rays are a form of electromagnetic radiation, not particles. They have less interaction with tissue so cause less damage and have a greater penetrative range in tissues.
The energy is emitted gamma rays is constant for a given radionuclide. They are valuable for diagnostic use, especially when radiation can be detected externally.
Describe the ideal properties for diagnostic radionuclides.
• Gamma ray emission only. o High abundance. o Reduced radiation dose to the patient. • For imaging studies, gamma energy 100 - 250 keV. o High detection efficiency. o No significant body attenuation. o Easy to shield. • Physical half-life approx. 1.5 times duration of test. • Simple, cheap and rapid production o Lack of radionuclidic impurities. o High specific activity. o Rapid production reduces operator dose. • Versatile chemistry. o To allow a range of labelling applications. • Chemical quantity – no pharmacological effect. • Radiochemically pure. o Biodistribution profile. o So only one energy is emitted. • Chemically stable. o Doesn’t break down in vivo. • Predictable biodistribution.
What is the most commonly used radioisotope for diagnostic radiopharmacy?
Technetium 99m.
How many different isotopes of technetium are there?
20.
What is the energy of the gamma ray emitted when 99Tcm degrades to 99Tc?
140 keV.
What is the half-life of technetium 99m?
6 hours.
What makes molybdenum and technetium seperatable?
Different physiochemical properties.
Where is the Mo99 used in Tc99 generators derived from?
The fission of U-235 in nuclear reactors.
Where are the main sites for Mo99 production found? Are there any sites in the UK?
The main sites for the production of Mo-99 are in Holland and South Africa, there are none in the UK.
Explain the technetium generator and how it is used.
This device contains a shielded glass column packed with alumna, to which Mo-99 (as its chemical form molybdate MoO4–) is strongly adsorbed.
This molybdate slowly decays to produce pertechnetate (TcO4-). Passage of saline through the alumina elutes pertechnetate and the sodium pertechnetate is used for one day.
How many Tc generators may be received by a site each week?
2.
What factors are taken into account when it comes to the choice of Tc generator?
This is based upon ease of operation, efficiency, safety profile, and cost.
List some practical points for the use of a Tc generator.
- Must swab collection vial’s rubber bung.
- Should elute in a grade A environment.
- Make sure collection vial has reached atmospheric pressure before removal - try to prevent aerosol production.
- Require shielding to protect the operator.
Can sodium pertechnetate be administered directly in this form?
Yes.
What is the most common indication for sodium pertechnetate?
Its most common indication is thyroid imaging; this is because it is preferentially taken up by the thyroid as molecules of sodium pertechnetate have a similar size and shape to iodide.
What can different chemistry of Tc lead to?
Different chemistry leads to different biodistribution so one can get different information from different parts of the body.
Pertechnetate is chemically stable, with Tc having a valency of +7. In order to make it react, what is needed?
One needs to alter the valency state of Tc. Oxidation states of -1 to +7 are known.
How does the BP define radionuclide purity?
‘The ratio, expressed as a percentage, of the radioactivity of the radionuclide concerned to the total radioactivity of the source’
What methods can be used to test the purity/identity of nuclides in the Tc generator?
- Molybdenum Breakthrough Test.
- Gamma Spectroscopy.
- Measurement of energies emitted.
- Measurement of the decayed sample.
- Determination of half-life.
Why is it hard to bind ligands to pertechnetate?
Here, all 7 electrons are shared with 4 oxygens; these oxygens are ‘big’, so a ligand is unable to get near to the Tc to bind.
Explain how tin ions in a radiopharmaceutical kit are used.
Tin ions in the kit are more reactive to oxygens, which take them from the TC, leaving it highly reactive (reduction). In this state one can attach to a ligand or the Tc may react with water to give Tc-colloid which is an impurity.
To prevent the Tc from reacting with oxygen in the air and reverting to pertechnetate, what is used?
Nitrogen-rich vials.
Outline the simple technique for the preparation of Tc radiopharmaceuticals?
The simple technique for preparation of Tc radiopharmaceuticals usually involves single addition of TcO4- to a kit which is a freeze-dried rubber capped vial containing all the required components. Addition of TcO4 dissolves the freeze-dried powder and a chemical reaction occurs.
What do simple Tc radiopharmaceutical kits include?
This includes ligand, reducing agent, buffers and stabilisers. In these kits, the most frequently used reducing agent is stannous chloride.
All manipulations of Tc radiopharmaceutical kits must be performed how?
Aseptically.
Why should preparation of radiopharmaceutical kits be kept as simple as possible?
Preparation should be kept as simple as possible so there is a little handling as possible leading to lower radiation exposure to staff and less change of microbial contamination.
To image the bones, what ligand is used?
To image bones, the methylene diphosphonate (medronate, MDP) ligand is used.
How does the MDP ligand work to image bones?
This ligand binds to hydroxyapatite Ca10(PO4)6(OH)2 therefor the greater the bone turnover, the greater the uptake of the ligand. Hence, it shows osteoblast activity.
This can detect changes before there are any changes in bone density.
What methods are used to assess radionuclide purity?
Column chromatography (HPLC) and planar chromatography.
What should the percentage of Tc-ligand be to pass quality control?
> 90%.
What should the percentage of free TcO4 and reduced Tc be to pass quality control?
<5%.
Which mobile phases are used for planar chromatography used to assess the purity of radionuclides?
- Butanone or acetone may be used to separate 99mTcO4 from the mixture.
- Saline used to separated 99mTcO4 and 99mTc-ligand from 99mTc-colloid.
Wy is QC needed with Tc radiopharmaceuticals?
Free TcO4- will be taken up in salivary glands, thyroid, and stomach. Reduced Tc goes to
liver and spleen - i.e. irradiation of unintended organs. This can also lead to sub-diagnostic images and possibly the need for more scans, increasing radiation dose.
What is lung perfusion imaging performed by?
Lung perfusion imaging is performed by IV injection of 99mTc MAA (macroaggregates of albumin - typically 30-50µm).
How does 99mTc MAA work?
These particles lodge in the terminal arterial-capillary bed of the lungs and this assesses blood supply.
Areas which show increased uptake of 99mTc MAA in lung perfusion imaging could be caused by?
- PE.
- Inflammation.
- Neoplasm.
- COPD.
Which other lung test is carried out at the same time as lung perfusion imaging?
Lung ventilation is also carried out in conjunction with perfusion.
Which radioisotope is often used for lung ventilation imaging?
81mKr.
Where does the 81mKr used in lung ventilation imaging come from?
This comes from a patient side generator from which the patient breathes to visualise the ventilation of the lungs. These generators have to be ordered in each day.
What alternative is there for 81mKr for lung ventilation imaging?
99mTc Technegas, which is expensive to buy but cheap to run.
If both the lung perfusion and ventilation imaging tests are done at the same time, what must be ensured?
That different isotopes are used to the two images can be differentiated.
Patchy uptake on perfusion and normal ventilation can be indicative of what?
PE.
What is the acquisition time for a lung scan?
20 mins.
What is the most common indication for a bone scan?
A most common indication for a bone scan is to assess bone metastases that are usually secondary to breast and prostate cancers.
