DESCRIPTION
DRYGEN The generator is a highly secure, automated system that allows you to easily obtain a sterile and pyrogen-free 99mTc as sodium pertechnetate. This solution is eluted from a chromatographic column alumina on which is fixed to the 99Mo from fission (half life: 66 hours) which generates the 99mTc (half life: 6.0 hours).
elution volume
The generator is designed to elute all the activity of 99mTc available in 5 mi. E 'can, however, elute with larger volumes (10 or 15 mi) in order to obtain various radioactive concentrations.
The generator is designed to elute all the activity of 99mTc available in 5 mi. E 'can, however, elute with larger volumes (10 or 15 mi) in order to obtain various radioactive concentrations.
ELUTION PROCEDURE - Before use, remove the plastic lid placed on top of the generator, thus making open the caps of the needles, which ensure sterility.
- Remove the cap site in the statement NaCl (input column) from its location (Fig. 1, A) and replace it with a bottle of eluent (0.9% NaCl, saline).
- Place a bottle under vacuum in a container shielded elution; eliminate the cap site in the words NaTcO4 (Fig. 1, B), place the bottle on the needle-protected, using the hole in the shielding and press up to full penetration in the center that houses the needle.
- Observe the appearance of bubbles in the bottle of saline solution.
- A waiting period of 3-5 min is sufficient to achieve complete elution.
If the bubbles do not appear within 15 sec by the insertion of container for elution, make sure the eluent bottle is securely engaged and that both needles are not blocked. If, despite everything, the elution does not, replace the bottle in a vacuum.
- With the completion of elution, the eluent fiacone leave blank spot checks to ensure the sterility of the needle.
- Remove the container and replace it with a new elution vacuum bottle (which requires no shielding), to remove any residual solution from the column and to protect the needle from contamination. The eluate should be used within 6 hours dall'eluizione.
CHARACTERISTICS OF THE FINAL SOLUTION
The solution of 99mTc-pertechnetate eluted from the generator is a clear, colorless, isotonic, sterile and pyrogen-free, at a pH between 4.5 and 7.5, according to the requirements of European and American pharmacopoeias.
The solution of 99mTc-pertechnetate eluted from the generator is a clear, colorless, isotonic, sterile and pyrogen-free, at a pH between 4.5 and 7.5, according to the requirements of European and American pharmacopoeias.
ACTIVITIES AVAILABLE
generators are available with
activities - from 2.5 GBq (67.5 mCi), expressed in 99Mo, corresponding to 2.2 GBq (59, 0 mCi) of Tc-99m in setting
- 25 GBq (675.0 mCi) expressed in 99Mo, equivalent to 21.9 GBq (591.0 mCi) of 99mTc in calibration.
intermediate doses are available on request.
generators are available with
activities - from 2.5 GBq (67.5 mCi), expressed in 99Mo, corresponding to 2.2 GBq (59, 0 mCi) of Tc-99m in setting
- 25 GBq (675.0 mCi) expressed in 99Mo, equivalent to 21.9 GBq (591.0 mCi) of 99mTc in calibration.
intermediate doses are available on request.
ELUTION KIT AND ACCESSORIES
Each generator is equipped with two elution kit according to the needs of the user that may be of different composition:
- Sep 5 Drygen
5 bottles of sterile and pyrogen-free 5.5-ml saline (0.9% NaCl) 10 empty bottles under sterile and pyrogen-free 20-mi.
- Sep 10 Drygen
5 bottles of sterile and pyrogen-free, 10.5 ml of saline (0.9% NaCl) 10 empty bottles under sterile and pyrogen-free 20-mi.
- Drygen Sep-15
5 bottles of sterile and pyrogen-free by 15.5 ml of saline (0.9% NaCl) 10 empty bottles under sterile and pyrogen-free 20-mi.Con the first delivery, we provide a portaflaconi shielded elution. A request has provided additional shielding where to put the generator on receipt.
QUALITY CONTROL
All generators are eluted and tested for operation, yield of elution, the eluate pH, 99Mo content in the eluate, contained in aluminum eluate, the eluate contained peroxide.
With random sampling (10-20% of production) generators are further checked for purity radionuclidic total radiochemical purity, sterility, pyrogen, non-toxic.
The general use of radionuclides with short half-life is made possible by the existence of portable generators, which it can be used over long distances from production sites, overcoming the limitations of time related to the preparation and quality control of branded products, transportation and storage. A generator is a system that contains a radionuclide "father" to the relatively long half-life nuclide, which decays into a "child", which is also radioactive, which is characterized by a short half-life and used immediately in the preparation of radiopharmaceuticals. The most widely used generator in nuclear medicine and what is based on the couple 99Mo/99mTc, built on a ion exchange chromatography column which provides for the adsorption by the alumina (Al2O3), the radionuclide "father", 99Mo, in the form molybdate anion (99MoO42-). The separation of technetium in the form of pertechnetate ion,-99TcO4, is passing through the column, a saline solution of NaCl (eluent). It is played on a different charge to separate the two anions: chloride ions exchange with the pertechnetate ions are soluble in saline, but not with molybdate, being insoluble, remains adsorbed on the column, thus obtaining a solution (eluate) of sodium pertechnetate (Na99mTcO4) that is collected from the bottom of the column, ready for use. The pertechnetate can also be separated from the molybdate extraction with methyl ethyl ketone (MEK), an aqueous solution containing two species: the pertechnetate passes in the organic phase while molybdate remains in the aqueous phase (liquid-liquid extraction generator).
Finally, the separation of 99mTc from 99Mo can exploit the fact that certain compounds of technetium sublimate at temperatures much lower than the corresponding compounds of molybdenum (generator sublimation).
figure is shown in the diagram in section of a typical 99m Tc generator, whose size are about 30 x 15 x 15 cm:
The operating mechanism is relatively simple: the molybdenum (atomic number 32) and Technetium (atomic number 43) are two chemically different, so you can choose a Resin Ion Exchange " with features that tie in an indissoluble way, Molybdenum, Technetium while leaving completely free. A sterile column of this resin is the "heart" of the generator
99Mo 99 mtc
it, after it was adsorbed on 99Mo, is introduced into a container of lead (gray, at the center of the drawing) of adequate thickness ( few cm) to stop the radiation from 99Mo, which are high energy (up to 1 MeV). The 99Mo decays with a half-life of 66.7 hours, 99mTc with a half-life of 6 hours, which in turn decays to 99Tc. On the pedestal, in the absence of external interventions, therefore, there are, in equilibrium, both 99Mo and 99mTc.
The post is externally connected by two tubes, starting from both ends of the same, they end up in as many needles fixed in the two chambers on the upper part of the generator. To elute the 99 MTC is sufficient to put one of the two needles in a glass vial with a pierceable rubber stopper, containing simple sterile saline; slips then the second needle in another vial, similar to the first but "vacuum" in turn contained in a shielded (lead or tungsten). The vacuum created by the vacuum causes the emptying of the saline vial that "washes" the column resin, removing the only 99 mtc that, after elution, it is all contained in the second vial, ready to be used to mark various radiopharmaceuticals (the 99Mo is trapped in the resin).
The quality of technetium obtained depends on the type of generator used and especially the choice of method of production of 99Mo. The 99Mo may in fact be produced in a reactor for neutron irradiation of molybdenum stable with (activated), but more often, is separated by common analytical techniques from radionuclides other elements with which it is mixed fission products in 235U. The molybdenum fission is accompanied by minor impurities, radionuclides and, compared to activation that also contains 98Mo is "carrier free", that is obtained with very high specific activity. This enables the use of columns of small size, lower volume of eluent active at high levels in the eluate. The generators are particularly sensitive systems, but improper use can affect the performance in terms of activities and may establish the exact cause "far" from low yields of marking.
The quality of the pertechnetate solution is, in fact, closely related to the presence in the eluate, a particular chemical species, as well as, the variability of some chemical and physical parameters such
* Hair:
as noted, the base of the marking there is a redox reaction involving chloride stannous (reducing species that is oxidized) and 99TcO4-(oxidant species that is reduced). The possible presence of other oxidizing agents reducing power subtracts the reaction system so that not all of the pertechnetate is reduced, remained free in the oxidized form (chemical impurity in the eluate that generates radiochemical impurity in the final radiopharmaceutical). The generator is eluted with normal saline solutions free of bacteriostatic (Inhibiting the growth of bacteria), since their oxidizing action may interfere with the redox reaction of the next phase of marking. Some disinfectants containing oxidizing agents and thus, for the operations of elution, sterilization (needles, caps, bottles) and any dilution of the eluate, it is advisable to use components already sterilized kit that typically accompany the generator.
* pH:
the 99Mo is adhered to the column at low pH (2-3), but after repeated washings with saline, this parameter settles in a range between 4 and 8, it is advised check at least on the first elution of each batch (quality control).
* Channeling:
phenomenon due to the formation of preferential channels during elution. In this way, not the whole column of alumina is affected by the action of the eluent resulting in reduced yields of extraction (generator dry.)
* Autoradiolisi:
this phenomenon is accompanied by the formation of free radicals that attack components of the generator, especially if there is water in the system (generator wet). Free radicals can cause breakage of the molecule of alumina resulting in the presence of aluminum ions in the eluate (chemical impurity). Free radicals can lead to reduced, insoluble forms of Technetium, that are extracted from the column with consequent reduction in yield of elution; reduced technetium species are also found in the flowthrough (radiochemical impurities). Some radiolytic products (eg, H2O2) have a high oxidizing power.
99Mo *:
radionuclidic eluate is the main impurity, may be accompanied by other fission products from 235U as 103Ru, 131I, 132I and 132Te (from 132Te), but only 99Mo is present in such quantities as to be routinely shown.
99Tc *:
is the carrier of 99mTc and comes both from the decay of metastable technetium, is direttamentedal decay of 99Mo (8%). The two forms, 99Tc and 99mTc, are characterized by the same chemical behavior, and both are present in the eluate as the pertechnetate ion (99TcO4 99mTcO4-e-).
In the processes of oxidation and labeling, there is a real competition between the two isomeric species in relation to the reducing agent and substrate, translated in low yields of marking. The most stable "moves" that metastable equilibrium reaction, and this phenomenon is all the more striking because the higher the concentration of-99TcO4. The presence of the carrier weight is already important in the eluate after elution from the last 24 hours (5 * 10-8 g per 3700 MBq of 99Mo). The problem can become critical if the time elapsed since elution increases (as in the case of the first elution after the weekend or after the time elapsed from the date of manufacture and delivery of the generator).
Quality Control of Technetium generator
All generators are eluted and tested for operation, yield of elution, the eluate pH, 99Mo content in the eluate, contained in aluminum eluate, the eluate contained peroxide.
With random sampling (10-20% of production) generators are further checked for purity radionuclidic total radiochemical purity, sterility, pyrogen, non-toxic.
The general use of radionuclides with short half-life is made possible by the existence of portable generators, which it can be used over long distances from production sites, overcoming the limitations of time related to the preparation and quality control of branded products, transportation and storage. A generator is a system that contains a radionuclide "father" to the relatively long half-life nuclide, which decays into a "child", which is also radioactive, which is characterized by a short half-life and used immediately in the preparation of radiopharmaceuticals. The most widely used generator in nuclear medicine and what is based on the couple 99Mo/99mTc, built on a ion exchange chromatography column which provides for the adsorption by the alumina (Al2O3), the radionuclide "father", 99Mo, in the form molybdate anion (99MoO42-). The separation of technetium in the form of pertechnetate ion,-99TcO4, is passing through the column, a saline solution of NaCl (eluent). It is played on a different charge to separate the two anions: chloride ions exchange with the pertechnetate ions are soluble in saline, but not with molybdate, being insoluble, remains adsorbed on the column, thus obtaining a solution (eluate) of sodium pertechnetate (Na99mTcO4) that is collected from the bottom of the column, ready for use. The pertechnetate can also be separated from the molybdate extraction with methyl ethyl ketone (MEK), an aqueous solution containing two species: the pertechnetate passes in the organic phase while molybdate remains in the aqueous phase (liquid-liquid extraction generator).
Finally, the separation of 99mTc from 99Mo can exploit the fact that certain compounds of technetium sublimate at temperatures much lower than the corresponding compounds of molybdenum (generator sublimation).
figure is shown in the diagram in section of a typical 99m Tc generator, whose size are about 30 x 15 x 15 cm:
The operating mechanism is relatively simple: the molybdenum (atomic number 32) and Technetium (atomic number 43) are two chemically different, so you can choose a Resin Ion Exchange " with features that tie in an indissoluble way, Molybdenum, Technetium while leaving completely free. A sterile column of this resin is the "heart" of the generator
99Mo 99 mtc
it, after it was adsorbed on 99Mo, is introduced into a container of lead (gray, at the center of the drawing) of adequate thickness ( few cm) to stop the radiation from 99Mo, which are high energy (up to 1 MeV). The 99Mo decays with a half-life of 66.7 hours, 99mTc with a half-life of 6 hours, which in turn decays to 99Tc. On the pedestal, in the absence of external interventions, therefore, there are, in equilibrium, both 99Mo and 99mTc.
The post is externally connected by two tubes, starting from both ends of the same, they end up in as many needles fixed in the two chambers on the upper part of the generator. To elute the 99 MTC is sufficient to put one of the two needles in a glass vial with a pierceable rubber stopper, containing simple sterile saline; slips then the second needle in another vial, similar to the first but "vacuum" in turn contained in a shielded (lead or tungsten). The vacuum created by the vacuum causes the emptying of the saline vial that "washes" the column resin, removing the only 99 mtc that, after elution, it is all contained in the second vial, ready to be used to mark various radiopharmaceuticals (the 99Mo is trapped in the resin).
The quality of technetium obtained depends on the type of generator used and especially the choice of method of production of 99Mo. The 99Mo may in fact be produced in a reactor for neutron irradiation of molybdenum stable with (activated), but more often, is separated by common analytical techniques from radionuclides other elements with which it is mixed fission products in 235U. The molybdenum fission is accompanied by minor impurities, radionuclides and, compared to activation that also contains 98Mo is "carrier free", that is obtained with very high specific activity. This enables the use of columns of small size, lower volume of eluent active at high levels in the eluate. The generators are particularly sensitive systems, but improper use can affect the performance in terms of activities and may establish the exact cause "far" from low yields of marking.
The quality of the pertechnetate solution is, in fact, closely related to the presence in the eluate, a particular chemical species, as well as, the variability of some chemical and physical parameters such
* Hair:
as noted, the base of the marking there is a redox reaction involving chloride stannous (reducing species that is oxidized) and 99TcO4-(oxidant species that is reduced). The possible presence of other oxidizing agents reducing power subtracts the reaction system so that not all of the pertechnetate is reduced, remained free in the oxidized form (chemical impurity in the eluate that generates radiochemical impurity in the final radiopharmaceutical). The generator is eluted with normal saline solutions free of bacteriostatic (Inhibiting the growth of bacteria), since their oxidizing action may interfere with the redox reaction of the next phase of marking. Some disinfectants containing oxidizing agents and thus, for the operations of elution, sterilization (needles, caps, bottles) and any dilution of the eluate, it is advisable to use components already sterilized kit that typically accompany the generator.
* pH:
the 99Mo is adhered to the column at low pH (2-3), but after repeated washings with saline, this parameter settles in a range between 4 and 8, it is advised check at least on the first elution of each batch (quality control).
* Channeling:
phenomenon due to the formation of preferential channels during elution. In this way, not the whole column of alumina is affected by the action of the eluent resulting in reduced yields of extraction (generator dry.)
* Autoradiolisi:
this phenomenon is accompanied by the formation of free radicals that attack components of the generator, especially if there is water in the system (generator wet). Free radicals can cause breakage of the molecule of alumina resulting in the presence of aluminum ions in the eluate (chemical impurity). Free radicals can lead to reduced, insoluble forms of Technetium, that are extracted from the column with consequent reduction in yield of elution; reduced technetium species are also found in the flowthrough (radiochemical impurities). Some radiolytic products (eg, H2O2) have a high oxidizing power.
99Mo *:
radionuclidic eluate is the main impurity, may be accompanied by other fission products from 235U as 103Ru, 131I, 132I and 132Te (from 132Te), but only 99Mo is present in such quantities as to be routinely shown.
99Tc *:
is the carrier of 99mTc and comes both from the decay of metastable technetium, is direttamentedal decay of 99Mo (8%). The two forms, 99Tc and 99mTc, are characterized by the same chemical behavior, and both are present in the eluate as the pertechnetate ion (99TcO4 99mTcO4-e-).
In the processes of oxidation and labeling, there is a real competition between the two isomeric species in relation to the reducing agent and substrate, translated in low yields of marking. The most stable "moves" that metastable equilibrium reaction, and this phenomenon is all the more striking because the higher the concentration of-99TcO4. The presence of the carrier weight is already important in the eluate after elution from the last 24 hours (5 * 10-8 g per 3700 MBq of 99Mo). The problem can become critical if the time elapsed since elution increases (as in the case of the first elution after the weekend or after the time elapsed from the date of manufacture and delivery of the generator).
Quality Control of Technetium generator
- Purity Molybdenum
- manufacturer's control (the presence of MO99, Tellurio132, Rutenio103)
2. purity of technetium (periodic)
- Bacterial Contamination
- ph
- contamination by molybdenum
- Presence of Tc99
- presence of aluminum ions
Use of technetium generators second POS
- Data retention on the register
- certification of the integrity of incoming generator
- controls first elution
- Diary of elution and quality features found
- identification data on the vial elution time, date, activity, volume, operator.
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