Technetium-99m generator By: NOR SYAKIRAH BINTI ABD MUTALIB

INTRODUCTION Technetium-99m (chemical symbol Tc-99m) is a metastable form of radioisotope Tc-99 widely used in nuclear medicine. Technetium-99m when used as a radioactive tracer can be detected in the body by medical equipment such as gamma cameras. It is well suited to the role because it emits readily detectable 140 keV gamma rays. It is a decay product of its parent nuclide Mo-99 and has a half-life of 6.02 hours. The short physical half-life of the isotope and its biological half-life of 1 day (in terms of human activity and metabolism) allows for scanning procedures which collect data rapidly but keep total patient radiation exposure low. The same characteristics make the isotope suitable only for diagnostic but never therapeutic use.

Technetium-99m was discovered in 1937 as a product of cyclotron bombardment of molybdenum. This procedure produced molybdenum-99, a radionuclide with a longer half-life (2.75 days), which decays to Tc-99m. At present, molybdenum-99 (Mo-99) is used commercially as the easily transportable source of medically used Tc-99m.

Tc-99m GENERATOR Tc-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. Instead its parent nuclide Mo-99 is supplied to hospitals after its extraction from the neutron-irradiated uranium targets.  It is shipped by specialised radiopharmaceutical companies in the form of Tc-99m generators. The generators, colloquially known as a moly cows, are devices designed to provide radiation shielding for transport and to minimize the extraction work done at the medical facility. These generators' output declines with time and must be replaced weekly, since the half-life of Mo-99 is still only 66 hours.

Source: The National Academies Press Plot of typical Mo-99 and Tc-99m activity on a logarithmic scale versus time for multiple elution of a technetium generator. Source: The National Academies Press

TYPES OF GENERATORS Column generator (most widely used commercially) - Dry type - Wet type Solvent generator Heat generator

Wet-type generator Dry-type generator

Source: IAEA Human Health Campus Components Column, usually glass, contains a bed of aluminium oxide (alumina) as a support for the parent radionuclide. Tubing allows the column to be washed with a sterile saline solution. Filters will be found in generators in the form of porous frits, which serve to contain the alumina within the column, and usually a 0.22 µm filter which serves to remove any small particles from the eluted sample and to act as a safety device to ensure a sterile product. Lead shielding is required for operator safety. All generators will provide a lead shield around the column and outlet tubing. Generators are contained in a plastic housing and have some method (handles, straps) to allow manual or mechanical lifting and positioning. Source: IAEA Human Health Campus

ELUTION PROCESS The process of “milking” Tc-99m is called elution. Mo-99 in the form of molybdate, MoO42- is adsorbed onto acid alumina (Al2O3). When the Mo-99 decays it forms pertechnetate TcO4-, which, because of its single charge, is less tightly bound to the alumina. Pouring 10mL of isotonic saline solution through the column of Mo-99 elutes the soluble Tc-99m, resulting in a saline solution containing the Tc-99m as the pertechnetate, with sodium as the counterbalancing cation. The solution of sodium pertechnetate may then be added in an appropriate concentration to the organ-specific pharmaceutical to be used. A large percentage of the Tc-99m generated by a generator is produced in the first 3 parent half-lives, or approximately one week.

Each eluate of the generator should not contain more than 0 Each eluate of the generator should not contain more than 0.0056 MBq, 0.15 μCi of Mo-99 per 37 MBq, 1 mCi of Tc-99m per administered dose at the time of administration, and not more than 10 μg of aluminum per mL of the generator eluate, both of which must be determined by the user before administration.

An elution vial

PRECAUTIONS and reminders Tc-99m generators received in advance of the calibration date and time will contain higher amounts of radioactive material. Care should be taken to assure that the generator is properly shielded. As in the use of any radioactive material, care should be taken to minimize radiation exposure to the patient and to ensure minimum radiation exposure to occupational workers. Since the eluate does not contain an antimicrobial agent, it should not be used after 12 hours from the time of generator elution. The generator should not be used after 16 days from the date and time of calibration. At time of administration, the solution should be crystal clear.

DISPOSAL OF GENERATORS Users should monitor the amount of radioactivity present prior to disposal of the unit. Storage and /or disposal of the Tc-99m generator should be in accordance with the conditions of Agreement State or Licensing State licenses and regulations, or other regulatory agency authorized to license the use of radionuclides. Vials and needles used for eluting may be discarded after two (2) days. Tc-99m generators should not be discarded in ordinary trash within 70 days of the calibration date. Tc-99m generators of ≤153.2 GBq, 4140 mCi may be returned to the manufacturer, while those of 183.9-614.2 GBq, 4970-16600 mCi must be returned to the manufacturer.

REFERENCES Amersham Healthcare. 1997. Technetium Tc 99m Generator For the Production of Sodium Pertechnetate Tc 99m Injection. Illinois. IAEA Human Health Campus. Design principles of the 99Mo → 99mTc radionuclide generator. http://nucleus.iaea.org/HHW/Radiopharmacy/VirRad/Eluting_the_Gen erator/Generator_Module/Design_principles/index.html [2 July 2014]. The National Academies Press. 2009. Medical Isotope Production Without Highly Enriched Uranium. Washington, DC.