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Radiopharmaceuticals — an overview of the basic principles

Radiopharmaceuticals are medicinal products which, when ready for use, contain one or more radioactive isotopes. When used for diagnosis, radiopharmaceuticals typically elicit no physiological response from the patient.1 A radiopharmaceutical can be either an isotope combined with a “kit” (see below) or an isotope alone.

By James Thom, DipRadSci, MRPharmS

In the UK, most large hospitals will have  their own dedicated radiopharmacy that prepares radiopharmaceuticals. However, due to the costs of operating a radiopharmacy and a lack of trained staff many hospitals are now purchasing their supplies from larger commercial or centralised radiopharmacies.

What is a kit?

A kit is a prepacked set of sterile ingredients designed for the preparation of a specific radiopharmaceutical. It contains a mixture of ligand, reductant, antioxidants, buffers and other components that, when mixed with a radioactive isotope, produces the required product.2

Kits are commercially available and are the preferred method for the production of radiopharmaceuticals, since they are a “closed” system (ie, neither the ingredients nor the final solution are exposed to the external environment).2

The alternative is to make preparations in-house — this can involve complex processes, in which the ingredients or semi-finished products are exposed to the atmosphere (ie, not closed in a vial, syringe or other sealed container). There is therefore a theoretical risk of microbial contamination and spillage.2

Technetium 99m

The isotope of choice for routine labelling of kits for diagnostic work is technetium 99m (99mTc). It has a gamma photon emission that is compatible with the requirements of a gamma camera, and no beta emission, so radiation exposure for the patient is minimised. The chemical properties of 99mTc also mean that it binds well to the tracers contained in the kits.

The half-life of 99mTc is 6.02 hours (ie, the time required for the isotope to decay to one half of its original radioactivity). However, its biological half-life is shorter because it undergoes rapid renal clearance. This is advantageous because any radiopharmaceutical that has not been absorbed by the target organ is cleared from the body and this results in high-quality images.

The dose of 99mTc that is administered depends on the radiopharmaceutical kit being used, the organ being imaged and the test performed. Doses are set out in the Administration of Radioactive Substances Advisory Committee’s “Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources”.3

Calculating doses for children requires special consideration since they have rapidly growing and dividing tissue that may be more sensitive to ionising radiation (eg, infants have a higher uptake in bone).4 Additionally, a young child’s organ-size-to-body ratio can be different from that of an older child or adult. These factors, along with the possibility of somatic and hereditary adverse effects that can result from small amounts of administered radioactivity, must be balanced against the possible benefits of any investigation.4 Each department should have a policy that addresses dosing for such patients.

Other radioisotopes are also used (eg, indium 111, iodine 123, selenium 75, fluorine 18) but are outside the scope of this article.


Various 99mTc radiolabelled kits are used for imaging different organs, some of which are outlined below.


Kits containing bisphosphonates (eg, medronate) that are labelled with 99mTc are used to detect areas of rapidly metabolising bone (eg, bone with metastatic growth or undergoing fracture repair).

For a standard bone scan the radiopharmaceutical is usually injected into a peripheral vein and the patient is imaged about two or three hours later. This allows time for the osteoblasts to incorporate the radiolabelled bisphosphonate into the bone.

All bone is in a state of turnover so the whole skeleton will be visible on the bone scan. However, the radiopharmaceutical is preferentially taken up into areas of rapidly metabolising bone so these areas will be more visible on the scan.


There are three main radiopharmaceutical products used to image the kidneys, each used for different indications.

Radiolabelled mercaptoacetyl triglycine (Mag-3; mertiatide) is used to assess renal blood flow and function. In addition to generating pictorial scans, Mag-3 scanning also produces graphical data representing renal function. Mag-3 is excreted mainly via tubular extraction, although some 11% is excreted via glomerular filtration. Blood clearance is rapid and renal excretion is close to 70% after 30 minutes and 94% after three hours. This improves the quality of the images (because the target-organ-to-background ratio is better), reduces the time taken to conduct the scan and minimises patient exposure to radiation.

Radiolabelled diethylenetriamine pentaacetic acid (DTPA; pentetate) is excreted via glomerular filtration and it can therefore be used to measure glomerular filtration rate. This test is often used to assess renal function before or during a course of nephrotoxic chemotherapy, and to adjust chemotherapy doses if required.

Radiolabelled dimercaptosuccinic acid (DMSA; succimer) is used for morphological studies of the renal cortex, individual kidney function and to locate an ectopic kidney.


Kits containing 99mTc-labelled exametazime are used to assess blood flow within the brain after stroke or in neurological conditions such as epilepsy, Alzheimer’s disease and migraine. It is an uncharged lipophilic product that, because of its low molecular weight, is able to cross the blood brain barrier. Maximum uptake of 99mTc-labelled exametazime into the brain occurs within one minute of injection and, at best, 7% of the injected dose reaches the brain. Typically, patients require no specific preparation for this test.


There are two 99mTc-labelled products that are used commonly in the UK for cardiac imaging: tetrofosmin and sestamibi. Such cardiac imaging can be used to assess the severity of myocardial infarction and identify the location of areas of cardiac ischaemia. Images are obtained when a patient is at rest and after cardiac “stress” (eg, after a patient runs on a treadmill or after administration of drugs such as adenosine or dobutamine).  

Very little of the injected dose of 99mTc is taken up into the myocardium — 1.2% of the administered dose is taken up at rest and 1.5% during cardiac stress. Irreversibly damaged myocardial cells do not take up the radiopharmaceutical and, therefore, areas of low/no uptake indicate areas of cardiac damage.

The scan should occur about one hour after the radiopharmaceutical is injected, during which time the patient should eat a light, fatty meal or drink one or two glasses of milk. This promotes hepatobiliary clearance of the radiopharmaceutical, which results in a better image (because any radioactivity that is not in the cardiac tissue will be eliminated).

Before using tetrofosmin or sestamibi patients must stop taking certain medicines. Typically nitrates, beta-blockers and calcium channel blockers should be stopped at least 24 hours before the test (although department protocols can vary).

Patients should not consume caffeine-containing drinks from midnight the day before the test. This is because caffeine is a competitive antagonist of adenosine, which is often used to induce cardiac stress during the test. If the effect of adenosine on the myocardium is reduced, the results of the images obtained will be less accurate. Accidental consumption of caffeine is a common reason for these tests being cancelled at short notice.


Radiolabelled kits can be used to conduct lung scans that are used to diagnose pulmonary embolism. A lung scan comprises two parts — a perfusion scan and a ventilation scan — and a diagnosis is made by comparing the two.

The perfusion scan involves injecting 99mTc-labelled macroaggregated albumin into a peripheral vein. The particles of macroaggregated albumin are carried to the capillary tree of the pulmonary artery system. The particles do not penetrate the lung tissue but are distributed evenly in the lung capillary bed and therefore result in an image that represents lung perfusion — reduced flow will be represented by areas with fewer particles and therefore less radiation. The length of time the particles remain in the lung depends on the particle size, with larger particles having a longer biological half-life.

For the ventilation scan, patients are scanned during or after inhaling radioactive krypton gas or an aerosol of 99mTc-labelled DTPA. The resulting image shows where air circulates in the lungs. Aerosols of radiolabelled DTPA tend to be used more commonly because aerosol generation devices produce a consistent particle size and 99mTc is readily available in most radiopharmacy departments.  

Adverse reactions

Adverse reactions to radiopharmaceuticals are very rare overall. They can include: dry mouth; rash on the neck, arms or chest; urticaria; sore, swollen lips; oedema of the face and eyes; dizziness; sweating; nausea and vomiting; headache; and lethargy. Most reactions that are reported have occurred with the use of bone imaging preparations, probably because these are the most frequently used.

  1. The Medicines Act 1968 (Application to Radiopharmaceutical-associated Products) Regulations. London: HMSO; 1992. (accessed 3 June 2011).
  2. Theobald T. Sampson’s Textbook of Radiopharmacy. 4th edition. London: Pharmaceutical Press; 2011.
  3. Administration of Radioactive Substances Advisory Committee. Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. March 2006. (accessed 3 June 2011).
  4. International Commission on Radiological Protection.  Radiation dose to the patient from radiopharmaceuticals. Annals of the ICRP 1988;18:issues 1–4.


James Thom is a radiopharmacist at University Hospital Southampton NHS Foundation Trust.


Studying this article will help you gain a better understanding of:

  • The pharmacological management of ADHD and National Institute for Health and Clinical Excellence guidance
  • Monitoring of medicines used to treat ADHD
  • Counselling points for patients with ADHD and their carers

For discussion

  • Do you know what conditions radiopharmaceuticals can be used to diagnose?
  • Do you know where to get information about the use of radiopharmaceuticals in your organisation? 

Test yourself

1    What is the most commonly used radioisotope for diagnostic imaging?

a)    Iodine 123
b)    Indium 111
c)    Selenium 75
d)    Technetium 99m
e)    Fluorine 18

2    Why is a light, fatty meal or a glass of milk given to patients before conducting tetrofosmin or sestamibi scans?

a)    To stop patients feeling hungry
b)    To aid hepatobiliary clearance of the radiopharmaceutical
c)    To ensure patients sleep during the scan
d)    To reduce gastric upset
e)    To avoid vaso-vagal reactions

3    Which of the following is often used to image the kidneys?

a)    Tetrofosmin
b)    Medronate
c)    Macroaggregated albumin
d)    Exametazime
e)    Mertiatide

4    Which of the following drugs are usually stopped 24 hours before patients receive sestamibi for cardiac imaging?

a)    Beta-blockers
b)    Nitrates
c)    Calcium channel blockers
d)    Answers a and b are correct
e)    Answers a, b and c are correct

5    Which of the statements about adverse effects of radiopharmaceuticals is true?

a)    They include dry mouth, rash and dizziness
b)    They are most often reported following the use of bone imaging products
c)    They are common
d)    Answers a and b are correct
e)    Answers a, b and c are correct

See PDF for answers

Citation: Clinical Pharmacist URI: 11092577

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