Product reconstitution Flashcards
How does radiolabelling occur
- All 99m-Tc radiopharmaceuticals are labeled by the formation of a covent or coordinate covalent bond
- incorperate a radionuclide into a molecule that has a known biological role
What does a typical 99m-Tc kit contain
- A radiopharmaceutical kit (cold kit) consists of a sterile reaction vial which contains the non-radioactive chemicals necessary to produce a specific radiopharmaceutical
- ligand/chelate
- reducing agent
- antioxidants
- stabilizers
- buffers
- may contain transfer ligands
Coordinating ligand
- AKA coplexing agent
- determines localization of technetium in the body
- complexes reduced 99m-Tc and 99-Tc to form RP
- May also complex Sn 2+ and Sn 4+
- The amount of complexing agent found in kits is 10-20 times more than the amount of tin
Ancillary chelating agent
- temporarily complex with tin and technetium when 99m-Tc cannot act as the complexing agent
Donor/exchange ligand
- chelating agent that forms a weak complex with reduced technetium to protect against disproportionation and hydrolysis
- helps when the reaction rate with the ligand is slow
Reducing Agent
- Facilitates the reduction of pertechnetate so it will bind to other chemical species
- The amount of stannous ion required for reduction is small, but a larger quantity of tin is added to ensure complete reduction of the pertechnetate
- The ratio of Sn 2+ to 99m-Tc atoms may be as large as 1 million
- SnCl2 prevents hydrolysis of tin and technetium
- improved bond but with 99m-Tc and stable chemical
Stabilizers
- Used to maintain the integrity of the radiopharmaceutical
- extremely important if the kit is used of a long periodof time, kits with a long shelf life and/or slow reaction times
- i.e. ascorbic acid, citrates, gelatin (sc kits)
Anitbacterial agents
- Used to prevent bacterial growth and reduce radiolysis
- not usually added to radiopharmaceutical kits
- i.e. 2% ethanol or 0.9% benzyl alcohol
Antioxidants
- Neutralize free radicals by donating electrons
- PABA, Melthylene blue, reducing agents
Acids/buffers
- pH is extremely important for the stability of biological properties of RPs
- Maintenance of optimum pH is archived by adding acidic, alkali or suitable buffers
- the ligand itself may act as a buffer
Carriers
- nuclides that are intentionally added to products to facilitate the recovery process
Carrier free
the radionuclide is not contaminated with any other stable or radioactive nuclide of the same element
No carrier added
- no carrier has been intentionally added to the radionuclide
Carrier added
- A carrier is intentionally added to the radionuclide
Specific activity
- Radioactivity per unit weight of radionuclide or labeled compound
- expressed as mC/mg or Bq/g
- A carrier-free sample of radionuclide has a high specific activity
- it is not always possible to produce carrier-free radionuclides
- will specify on product monograph if not carrier free
Why is it desirable to obtain a high specific activity
only a small mass of the radionuclide is administered to the patient- less chance of the patient having a pharmacologic response
Specific concentration
- The radioactivity per uni volume of diluent
- expressed as mCi/mL or MBq/mL
Describe cold kit preparation
- prepared by adding an scidified atannous chloride solution to the complexing agent at a specific pH
- Any additional substances are added
- aliquots of the completed mixture are dispensed into sterile reaction vials and frozen
- it is thenl lyophilized under vacuum to remove all water (freeze dried)
- Vials are bacfilled with nitrogen or argon before sealing
- sterile equipment and aseptic techinques are followed under a lainar flow hood
Stannous
- prevents hydrolysisof tin and technetium
- improved bon with 99m-Tc and stable chemical
- excess in relation to amount of pertchnetate
- 1000 to a million times more Sn +2 to ensure a complete reduction
- readily oxidized in air and by dissolved oxygen resulting in free radicals and radiolysis
- dont add air to majority of kits
What occurs if too much tin is used
- increased chance of hydrolysis of the tin
- can result in the formation of 99m-Tc colloid or other tin complexes
- reduced bound product
What occurs is too little tin is used
- Leads to the incomplete redution of 99m-Tc to the appropriate oxidation state
- a low yield of the desired 99m-Tc complex with ‘free’ 99m-Tc
- The optimum ratio of complexing agent to tin depends on the kit
What does the addition of pertechnetate do to the lyophilized powder
- Causes the lyophilized powder to dissociate and intiate the reaction
- stannous complex reduces the oxidation state of the pertechnetate
- this allows the pertechnetate to bind to the complexing agent
What are the 3 species found in a labelled 99m-Tc RP kit
1) free 99m-Tc in the form of pertechnetate that has not be reduced by Sn2+
2) Hydrolyzed 99m-Tc in the form of 99m-Tc 02 that did not react with the chelating agents
3) Bound 99m-Tc in the form of the 99m-Tc complex, which is the desire out come
- QC should be performed on every kit to ensure radiochemical purity
Shelf-life
- lyophilized kits remain stable for several months prior to reconstitution
- Reconstituted kits have a shelf-life varying from 30 min to 18 hrs
- commonly 6 hrs
Free radicals
- present in free pertechnetate
- generated before/after reconstituion
- contain a single unpaire electron
- electron donated becomes a reducing agent
- electron accepted becomes an oxidizing agent
What do free radicals increase with
- Increasing activity
- time
- oxygen
- low concentrations of stannous
