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Selection of Labelling Kit

Introduction

In most 99mTc radiopharmaceuticals, the radionuclide technetium-99m (eluted from a technetium-99m generator) is bound to metal binding atoms of an organic molecule. In this way a technetium complex is formed and the biological properties of this complex determine for which clinical investigation the complex is useful.

For instance, when a bone scan has to be performed, a technetium-99m labelled diphosphonate is normally used as the tracer agent. This 99mTc-diphosphonate complex is taken up in the bone (and more so in pathological bone than in healthy bone). In very rare cases and in very few departments, fluorine-18 in the form of fluoride in combination with positron emission tomography (PET) is used for this purpose.

Which 99mTc labelled diphosphonate to use?


Different 99mTc-labelled diphosphonates are being used clinically for bone scans, of which the most common are:

  • 99mTc-medronate, also called 99mTc-MDP or 99mTc-methylene diphosphonate:

  • 99mTc-oxidronate, also called 99mTc-HDP or 99mTc-hydroxymethylene diphosphonate:

  • 99mTc-dicarboxypropane diphosphonate, also called 99mTc-DPD:


The complexes of technetium-99m with these diphosphonates have a similar biological behaviour, and, although not completely identical, they can be used for the same purpose.

Mechanism of uptake of 99mTc-MDP in the bone
The exact mechanism of uptake of technetium-99m labelled diphosphonates in the bone is not known. It is generally accepted that technetium-99m medronate localizes on the surface of hydroxyapatite crystals of bone by a process termed chemisorption, with blood flow and/or blood concentration being the most important factor in the successful delivery of the agent to sites of uptake. Visualization of osseous lesions is possible since skeletal uptake of technetium-99m medronate is altered in areas of abnormal osteogenesis (bone growth).


Indications for a bone scan
The main indications for a bone scan are visualisation of tumor metastasis in bone, osteomyelitis, fracture, stress fracture, avascular necrosis, osteoporosis, and prosthetic joint evaluation.
Diagnosis of metastatic disease is the most common indication: it has a 95% sensitivity and lesions are detected an average of 6 months earlier than with X-ray studies.

Normal bone scan Bone scan showing presence of metastasis


Labelling kits for the preparation of 99mTc-medronate (99mTc-MDP) or similar agents


To allow a fast preparation of 99mTc-MDP in the hospital (due to the short physical half-life of technetium-99m of 6.01 hours), labelling kits are available from different manufacturers. Details about these kits (e.g. trade name, manufacturer, nature and amount of ingredients) are summarized in this table.


Sodium oxidronate kit

Some of the trade names of such diphosphonate labelling kits are:
Technetium Tc99m Medronate For Injection, Technescan MDP,
Amerscan Medronate II Technetium Agent, Lenoscint,
Osteolite, MDP
Lenoscint kit
Technescan MDP kit

Usually, such kits contain 5-15 mg of MDP as the Tc-binding ligand, 0.5 mg of a stannous salt (mostly stannous chloride) to reduce technetium from valence 7 (in pertechnetate) to a lower oxidation state in which it can bind to the diphosphonate. In some cases an antioxidant such as ascorbic acid, 4-aminobenzoic acid, or gentisic acid is also included to prevent reoxydation of reduced technetium to pertechnetate. To assure a sufficiently long shelf life of the labelling kits, the ingredients are usually in lyophilised form. For more detailed information on the binding process, please see Radiolabelling with 99mTc and calculation of doses.



Package leaflet of a
labelling kit for the
preparation of
99mTc-MAG3
Refrigerator with labelling kits

Nuclear Medicine Departments will usually select one of the commercially available diphosphonate labelling kits for use in their clinical routine and will have a number of vials of this labelling kit in stock. Most labelling kits for the preparation of 99mTc labelled radiopharmaceuticals are stored in a refrigerator to enhance their stability. The package leaflet provides information on the required storage conditions of a particular labelling kit.

So, the radiopharmacist or technician who has to prepare the radiopharmaceutical for a bone scan doesn't need to make a selection from different diphosphonate labelling kits, but has just to take care that (s)he: selects the diphosphonate labelling kit out of the stored labelling kits (for the preparation of different 99mTc radiopharmaceuticals).

(S)he also needs to check that the expiry date mentioned on the vial and on the package has not yet passed and that the selected vial is not damaged in any way.

The expiry date of labelling kits is indicated on both the box and the vials


Watch a video of a Radiopharmacist selecting a kit.