Slide 1: Rdioisotoipes Generators Isotope Generator : : Isotope Generator : An isotope generator produces short-lived isotopes from the decay of long lived parent isotope.
Allows 24 hour availability of short lived isotope without the necessity of complex production procedures (e.g. cyclotron irradiation) Secular Equilibrium : Secular Equilibrium In a generator system where the half-life of the parent is so long , that the decrease of activity is negligible.
At secular equilibrium the activity of the daughter,, is equal to the activity of the parent,
An example of a generator which reaches a seqular equilibrium is the 68Ge/68Ga - generator, where the half-life of 68Ge and 68Ga is 275 days and 68 minutes respectively. Secular Equilibrium : Secular Equilibrium Transient Equilibrium : Transient Equilibrium If the half-life of the parent is longer (but not greatly longer) than the half-life of the daughter( 10 times ), of the daughter isotope reaches a transient equilibrium with the parent ( after about 4 daughter half lives). Transient Equilibrium : Transient Equilibrium An example of a generator system that exhibits a transient equilibrium is the 99mTc-generator. Isotope Generator : Isotope Generator A clinically useful isotope generator should have the following characteristics:
Produce a daughter with high radiochemical and radionuclidic purity.
Safe and simple to operate.
Produce a sterile and pyrogen-free eluant .
The daughter should be easily separated from the parent .
The chmical form of the eluant should be suitable for the preparaion of radiopharmaceuticals.
,,,,,The 99mTc-generator is the most commonly used isotope generator in nuclear medicine . 99mTc Generator : 99mTc Generator Mo99- Tc99m Generator : Mo99- Tc99m Generator Molybdenum-99 activity is obtained by (n,γ) activation of stable Molybdenum or by separation from reactor fission fragments ( Higher specific activity). 99mTc Generator : 99mTc Generator How long after a prior elution is the activity in the generator maximized ? 99mTc Generator : 99mTc Generator 99mTc Generator : 99mTc Generator How is the 99mTc extracted from the generator?
The 99Mo is adsorbed onto the alumina (Al2O3) column as (NH4)2 99MoO4 (ammonium molybdate).
99Mo exists in the 99MoO42- form (molybdate) having two ionic charges.
When 99Mo decays, it is transformed into 99mTc, which exists in 99mTcO4- form (pertechnetate), having one ionic charge . 99mTc Generator : 99mTc Generator Elution with isotonic saline saline removes the weakly bound 99mTcO4-, leaving the 99MoO42- on the alumina column.
The chemical form of 99mTc in the eluant is Na99mTcO4 (sodium pertechnetate) .
80% of the of the available Tc99m is extracted in a single elution. 99mTc Generator : 99mTc Generator The figure below is a schematic of a 99mTc generator. To extract the 99mTC, a saline charge is first connected to the generator. Then an evacuated vial is connected (collection vial). The vacuum in the collection vial will suck the saline through the generator column and extract the 99mTc. 99mTc Generator Quality Control : 99mTc Generator Quality Control 99Mo Breakthrough :
Aluminum Ion Breakthrough
Hydrolyzed reduced (HR) Tc : 99Mo Breakthrough :
Due to imperfections in the production of the alumina column, there is always a possibility that some 99Mo is removed from the column when the generator is eluated. In a functional generator the 99Mo breakthrough should be minimal .
In order to prevent that a patient injected with large amounts of 99Mo, the generator eluate has to be checked for the presence of 99Mo.
The presence of 99Mo is assayed by measuring the 740 and 780 keV gamma rays which 99Mo emits. These gamma-energies can be separated from the 140 keV gammas emitted from the de-excitation of 99mTc by placing a lead shield around the eluate, thick enough to absorb all these gammas( about 3 mm) . 99Mo Breakthrough : 99Mo Breakthrough This is the basic procedure for testing of 99Mo breakthrough (to be performed for each elution of the generator)
Placed the empty lead shield in the dose calibrator and zero the calibrator
Place the eluate in the lead shield and record the reading using the appropriate dial setting
Remove the lead and record the activity at the 99mTc setting
Value should be less than 0.15 uci Mo99 / mci Tc99m at time of adminstration. Slide 18: Other Contaminants
The amount of other contaminants in the eluate depends on the source of the 99Mo:
Neutron activated 99Mo
Produced from high purity 98Mo
Low specific activity
Small amounts of contaminants
Reactor produced 99Mo
99Mo is a product from fission of 235U
High specific activity
Contamination of other fission products: 134Cs, 131I, 239Np, 103Ru, 86Rb, 60Co, 124Sb Aluminum Ion Breakthrough : Aluminum Ion Breakthrough Every eluate should be checked for Al3+ impurities
Al3+ can cause a degradation in image quality due to poor incorporation of 99mTc into the tracer. NRC recommends:
20 µg Al3+/ml of eluate (for generators produced by thermal neutron activation)
10 µg Al3+/ml of eluate (for generators produced from fisson of 235U)
The test kit that measures Al3+ ion is special colometric test paper strip containing a chemical sensitive to the presence of aluminum ion at the microgram level
The test is performed by placing a drop of the eluate and a drop of a standard solution on the test strip and comparing the colors of the spots on the paper. Hydrolyzed reduced (HR) Tc : Hydrolyzed reduced (HR) Tc It is recommended that every eluate is checked for HR Tc HR Tc is a radiocolloid which is taken up in the liver and the spleen
The presence of HR TC in the eluate causes a degradation in image quality due to to poor incorporation of 99mTc into the tracer.
No legal limit but < 2% is appropriate value. Other tests : Other tests pH: 4.5-7.5
Check for pyrogenicity and sterility Other Radionuclide Generators : Other Radionuclide Generators Ga68- Ge68 Generator
Rb82- Sr82 Generator
In113m-Sn113 Generator What is the diffrence between Radionucldic purity, Radiochemical purity , Chemical purity and Biological purity of Radiopharmaceuticals? : What is the diffrence between Radionucldic purity, Radiochemical purity , Chemical purity and Biological purity of Radiopharmaceuticals? Radionucldic purity : Radionucldic purity Unwanted or different chemical forms containing the radionuclide of intrest.
e.g Colloid TcO2 if present with Tc99m pertechnitate.
Can be determined by paper chromatography.
The British Pharmacopia (BP) specifies that not less than 95% of the activity must be in the form of pertechnitate ion. Radiochemical purity : Radiochemical purity Presence of radionclides other than the one of intrest.
Accurate determination by Gamma spectrometry or by dose calibrator, Chemical purity : Chemical purity Non radioactive chemical species.
Aluminium ions ( Al 3 +) .
If exceeds the specified limit of 10 ug/ml may cause agglutination of RBC,s or aggregation of colloidal preparation.
Arise from degredation of the aluminia column.
Can be determined colorimetrically. Biological purity : Biological purity Concerned with presence of contaminating microorganisms ( sterility). Or products of their growth ( pyrogenicity)
Sterility tested by incubating for 14 days in a media proven to support the growth of anaerobic and aerobic organisms.
Pyrogens or endotoxins: by Limulus test : by using chromogenic peptide cleaved by endotoxins activation. Slide 28: Thank You