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A radiopharmaceutical labeled with Tc-99m is what, from the chemical point of view, is called composed of c oordinazione or complex. These species are always formed by a transition metal to which they are linked (coordinates) molecules are called ligands. Technetium is precisely the transition metal, while the ligands can be single atoms such as chlorine, bromine, oxygen, nitrogen, or actual molecules, such as ammonia, water, carbon monoxide, amino acids, which under certain conditions, bind to the metal. In a complex, the metal is then able to train a large number of links with many ligands. This number is called the coordination number or simply metal coordination. For example, the technetium can form complexes with coordination numbers 4,5,6,7.

The most common are 5 and 6. In Figure 1 two complexes are schematically represented with their coordinates 6 (hexacoordinated) and 5 (penta), with binding represented by symbols L or X . (Fig. 1)

Sometimes it may happen that two or more ligands coordinated to the metal, are in turn connected by a chain of atoms placed at appropriate bridge between them. The resulting binder, LL (or XL, XX) is called a bidentate ligand or chelating agent to underscore the fact that the two groups (L or X) are no longer independent of each other, but united indissolubly by the side chain (Fig. 2 ). It follows, therefore, that connections between three or four groups, giving rise to ligands tridentate ligands (LLL or LXL, etc.). tetradentati and (LLLL or LXLX, etc..), respectively. (Fig. 2)
octahedral geometries and pyramid with a square base are those that are found most frequently in the complex of technetium used in clinical practice as diagnostic agents. Another very imortante parameter for the characterization of a coordination compound, is the number (or state) of oxidation of the metal (technetium). This parameter has no physical meaning, and is attributed to the different atoms that make up the complex on the basis of purely formal rules. Not being able to go into here the illustration of these rules, it suffices to note that in the case of the atom of technetium, the knowledge of its oxidation state is used to determine the total electric charge of the complex and also to determine which is the most effective method of marking to reach the preparation of a particular radiopharmaceutical. Later we will just quote the oxidation state of technetium in different radiopharmaceuticals and use it to discuss the various methods of marking.

marking methods with Tc

Based on the above, for labeling with Tc-99m is more correctly understood the formation a complex of technetium with appropriate ligands. The nature of the ligands is a key parameter for determining whether a complex can be formed or not. The only requirement, which must necessarily satisfy a binder is to hold in its molecular structure an appropriate set of atoms that can bind firmly to the metal center. The rest of the molecule can be bonded, at least in principle, chosen at will. The radionuclide 99m Tc is obtained in saline solution in the form of pertechnetate anion, [4 99mTcO ] ^- . Using the terminology outlined above, it is possible to describe the anion [4 99mTcO ] ^{- 2 -} ) to form a very compact structure and tetrahedral geometry.

The oxidation state of technetium pertechnetate nell'anione is +7. It is the highest attainable state of oxidation of this metal is one of the most stable chemical species of technetium in aqueous solution. If you want to prepare a radiopharmaceutical from [99mTcO 4] ^- , coordinated with bonds to give the complex special biological properties, must be removed, in part or completely, the oxygen atoms bound to the metal and replace them with coordinated atoms of new ligands. During this process, the oxidation state of technetium undergoes decrease and their value, less than +7. Therefore, labeling with 99mTc-is represented in Figure 2.
as a coordination compound between the technetium and oxygen. The metal atom is bonded to four oxygen ligands (O

[99mTcO 4] ^- + R + L 99mTc-(L) n

(Schema2)

In the diagram above, L represents a ligand chosen properly, while R represents a species whose role is to lead to the reduction of technetium atom through the removal of oxygen atoms nell'anione pertechnetate to form the final assembly 99Tc (L) No As a species is most commonly used reducing agent stannous ion (Sn 2 + ) that is introduced in the form of a salt water solution of chloride (SnCl 2 ). The reaction can then be rewritten as follows:

In practice, all of Tc-99m radiopharmaceuticals, which have so far been introduced in clinical use, are prepared through the reaction shown in the diagram above. As the marking method described has the advantage that it can easily be applied under physiological and strictly sterile and pyrogen free. Also, you need a relatively low amount of SnCl 2 to achieve a complete reduction of technetium as pertechnetate dall'anione, an amount that generally does not create problems in the preparation or solubility or toxicity to the patient. The removal of oxygen atoms nell'anione [99mTcO 4] ^- , occurs through the formation of species Sn (OH) 4 (and other similar species), which binds oxygen in the pond OH group ^- away, in this way, technetium atom is then free to coordinate the ligand L. This has not only the aim of providing appropriate biological properties to the final assembly, but also to strongly stabilize the metal, so as not to allow it to recombine with oxygen atoms (present in aqueous solution) and to reform the pertechnetate anion, hydrogen peroxide or a secondary species which the technetium dioxide (TCO 2 ), which, being very soluble, it tends to form colloidal particles. The ligand L must be chosen from among those that have a higher coordinating ability towards the technetium. In this regard, it was seen that the chelate ligands (bidentate, tridentate, tetradnetati, etc..) Are among the most effective in forming stable complexes with technetium.
In conclusion, although the process shown in Figure 2, can be enriched in individual terms, with the addition of other species such as oxidizing compounds (eg. Ascorbic acid, sugar) or solubilizers (eg. Cyclodextrins), it is the most effective and convenient for the preparation of radiopharmaceuticals labeled with 99mTc.

The radiopharmaceutical sodium pertechnetate

99mTc decade in 99Tc, for internal transition with a T / 2 of 6.02 hours, emitting gamma radiation from 140 keV. In agreement with those reported in the various pharmacopoeias, the 99m can be achieved either 99Mo from the fission trigger in the form of sodium pertechnetate solution. The solution of Na 99m TcO 4 injection should be sterile, isotonic by adding NaCl, clear and colorless in appearance and at a pH between 4.0 to 8.0 and an activity between 90% - 110% of the activity of 99Tc declared. Its radiochemical purity must be> 95%, while a radionuclide impurities, must not be> 0.15% for the 99Mo and> 0.01% for other radionuclides range issuers. The presence of aluminum ion to be <> ^{4 -} is venous, where the ions pertechnetate remain in balance, partly free and partly bound to serum proteins. The free ions, due to their small size, leaving the vascular compartment and diffuses to the interstitial fluid, lower blood concentrations of pertechnetate , this implies a similar release of 99 TcO ^{4 -} protein bound. Once you arrive in the interstitial fluids, the pertechnetate is removed from various organs or systems: the stomach, thyroid, salivary glands, intestine, the choroid plexus, mucosa, kidney and vascular structures.
localization in gastric tissue ion pertechnetate is due to the fact that technetium is secreted form of acid in the stomach pertecnico . In fact, the cells of the stomach wall produce CO 2 giving rise to the carbonate ion, which, with the ion exchange pertechnetate , gives rise to acid pertecnico HTcO ₄ .

_{CO 2 + H} H 2 O + + HCO ₃ ^- + (99 MTCO 4) ^- H99 MTCO ₄ ^{- H + +99} MTCO ₄ ^-

pertechnetate ion , in the stomach, may also be reabsorbed by diffusion, when its blood concentration is less than that present in gastric contents. Part of pertechnetate passes into the stomach, where the tract is partly absorbed, through a phenomenon of transport. The LOCATION of pertechnetate in the thyroid is through transport proteins that are not able to distinguish ion pertechnetate solvated by iodide ion, since the ions are very similar, with regard to weight, size of the beam ion and the charge density. Consequently, 99 MTCO ₄ ^- is avidly taken up by thyroid cells, although these can not be organificato then, as with the iodide ion.
distribution in appearing brain is conditioned by the characteristic ion pertechnetate not distributed in the brain, with the exception of the choroid plexus. It can only see the vascular structures, as the blood-brain barrier prevents entry into the cellular compartment, except for focal areas in which it could have possibly determined the alteration of its permeability (cancer, inflammation, stroke).
localization in the salivary glands as you , as is the case for the thyroid, the similarity of the chemical and physical properties of this anion with those of other physiologically in saliva determines the ' salivary excretion. In conclusion, what happens at the end of the preparation is:

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Chemistry of Technetium Technetium Generator

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.

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.

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.

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

1. 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

1. 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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Technetium is a product of nuclear fission of natural and artificial ' and uranium is used in nuclear medicine for scintigraphic and tomographic images of various body compartments ( ^{99m Tc} ).

Carattaristiche

99m Tc to its short half-life (6.01 hours), to be a gamma ray emitter and the ability to bind to several molecules of biochemical interest ( radiopharmaceuticals) is used in medical tests radiodiagnosica based on radioactive isotopes (radionuclides ), in particular, in some imaging techniques such as scintigraphy bone.

Technetium-99 (99m)

For a number of reasons physical, chemical, biological and logistical, technetium 99m is an almost ideal basis for the preparation of most commonly used radiopharmaceuticals in diagnostic nuclear medicine. dalpunto physically the relatively short half-life of this radioisotope (6 hours) dicisivo factor for its widespread use.
Technetium-99 is the product of another son the radioisotope molybdenum-99. This isotope has a half life parent longer that 65 hours (3 days) compared to 6 hours of technetium-99m. The logistical aspect of such a situation is that distribution is permitted also, and especially large-scale deliveries of reaching generators in locations significantly distant from production. Molybdenum-99 is permanently attached to an inert support (eg particle aluminum), so that it can not go into solution. Technetium-99m, on the contrary, continuously produced by its decay (Mo99), is highly soluble and can then be easily eluted in a chromatographic system consisting of a column through which can pass a simple saline solution.

In this way the longer half-life radioisotopes (molybdenum-99m) will supply continuously, using this system, "generator", the with shorter half-life radioisotope (technetium-99m). The half-life corresponding to that of molybdenum-99 provides for a smooth distributions of Technetium-99m to all nuclear medicine located a reasonable distance from power.

A little 'History

Emilio Gino Segrè (Tivoli, February 1, 1905 - Lafayette, April 22, 1989) was an Italian physicist.

He studied physics at the University of Rome "La Sapienza", where he studied under Enrico Fermi, and where he obtained a professorship in 1928, and later became director of the Institute of Physics, University of Palermo (1936). In 1938, following the proclamation of the racial laws in Italy, emigrated to the United States and collaborated with the group of nuclear physicists Berkeley. Then worked at Los Ala mos and in 1946 returned to the University of California.

The researchers identified in a sample of molybdenum sent to them by Ernest Lawrence . The sample consisted of a piece of deflector in elttrostatico molybdenum that had been bombarded with nuclei of deuterium in cyclotron University of California of Berkeley , turning it into ⁹⁷ Tc. Technetium was the first artificially produced element in history, even if it subsequently proved its existence in nature both inside and outside the solar system .

For many years had been a gap in the periodic table instead of the number 43. Dmitri Mendeleev predicted that the missing element would be chemically similar to manganese and therefore ekamanganese baptized. In 1925 Noddack Walter and Ida Tacke , the discoverers of rhenium announced the discovery of element 43 masurium calling (from Mazury region of East Prussia, now Poland), but their ad was never confirmed and now commonly considered incorrect, Although some researchers have challenged this conclusion.

In 1952, technetium was identified by ' American astronomer Paul W. Merrill in the emission spectrum of some stars red giants , strengthening the theory that these stars produce heavy elements. It was also found small quantities in the uranium mines , especially in those where there have been phenomena natural nuclear fission, as in the natural nuclear reactor in Oklo .

In 1937, at Palermo, discovered technetium, then at Berkeley, the astatine, and helped with the production of plutonium. In 1955, using the betatron at Berkeley, was able to produce the antiproton, in collaboration with Owen Chamberlain. Together with the latter received the Nobel Prize for Physics in 1959. In 1974 he was appointed to the chair of nuclear physics at the University of Rome. So as we have just
saw the discovery of technetium dates back to 1937 when Carlo Perrier and Emilio Segrè (photo), who worked in Italy in the laboratories of the Institute of Physics, University of Palermo, were able to isolate the 97 Tc from a sample of molybdenum subjected to bombardment with deuterons (deuterium nuclei) in the cyclotron of the University of California at Berkeley.
component receives 43 was given the official name of technetium immediately after the end of World War II. It was the first artificially produced element in history. Technetium (Tc), a chemical element with atomic number Z = 43, belongs to the second set of metal transizione.Il Technetium is the lightest among the chemical elements is completely devoid of stable isotopes. It is made artificially in concentrations up to 6%, from the fission products of uranium-235 / 238 nuclear power plants.

are known as many as 25 isotopes whose atomic masses ranging from 86 to 118 atomic mass units. All isotopes of technetium are radioactive and have half-lives associated with very diverse: they range from the order of microseconds (eg 86m Tc) to the hundreds of thousands of years (eg 97 Tc, 98 Tc, Tc 99). Merrill in 1956 identified the 99 Tc in the emission spectrum of some red giants, thus fortifying the theories of nucleosynthesis of heavy elements in stars. Technetium-99 is the isotope most common and most readily available because it is the main product of fission of uranium-235. One gram of 99Tc produced 6.2 × 10 8 disintegration per second (0.62 GBq / g).

99mTc

Technetium-99 (99mTc) satisfies many requirements for its use of the water, because its radioactive emissions consists almost exclusively of gamma radiation with a single energy peak (140KeV), enough for good penetration through the body structures, so for a good detection from outside by current instrumentation (gamma-room). Moreover, its relatively short half-life (approximately 6 hours) can be administered to the individual patient to relatively high doses, while maintaining the radiobiological load to extremely low levels. This radioisotope is therefore currently the basis for wider use in the preparation of radiopharmaceuticals used in nuclear medicine for diagnostic conventional.

Technetium-99m is used in 20 million diagnostic nuclear medical Procedures Every year. Approximately 85 percent of Diagnostic Imaging Procedures in nuclear medicine use this isotope.

iso 99 m Tc	NA trace	Half- life 6.01 h	DM IT	DE (MeV) 0.142, 0.002	DP 99 Tc
			γ	0.140	-

Technetium-99m is made from the synthetic substance molybdenum-99 which is a by-product of nuclear fission. It is because of its parent nuclide, that technetium-99m is so suitable to modern medicine. Molybdenum-99 has a half-life of approximately 66 hours, and decays to Tc-99m, a negative beta, and an antineutrino (see equation below). This is a useful life since, once this product (molybdenum-99) is created, it can be transported to any hospital in the world and would still be producing technetium-99m for the next week. The betas produced are easily absorbed, and Mo-99 generators are only minor radiation hazards, mostly due to secondary X-rays produced by the betas (also known as bremsstrahlung ).

⁹⁹ Mo (Negative Beta Decay) → ^99m Tc + β ^- + ν

Where β ^- = a negative beta particle (electron), and ν = an antineutrino.

^99m Tc will then undergo an isomeric transition to yield ⁹⁹ Tc and a monoenergetic gamma emission.

^99m Tc → ⁹⁹ Tc + γ

When a hospital receives molybdenum-99 generator, the technetium-99m from within can be easily chemically extracted. That same molybdenum-99 generator (holding only a few micrograms) can potentially diagnose ten thousand patients because it will be producing technetium-99m, strongly for over a week. The radioisotope is perfect for medicinal purposes. The short half life of the isotope allows for scanning procedures which collect data rapidly. The isotope is also of a very low energy level for a gamma emitter. Its ~140 keV of energy make its use very safe and Substantially reduces the chance of ionization.



Technetium (Tc) plays an important role in modern medicine as one of its isotope, technetium-99 metastable the (Tc-99m) is, to date, the main radionuclide used in the diagnostic field. Currently, more than 90% of the nuclides used in standard diagnostic procedures in nuclear medicine, is based on the use of 99m Tc. Its widespread use is due to the fact that, before it was available, all radionuclides were produced in only a few large nuclear centers (mainly in the U.S. and Canada) which was shipped by air to individual laboratories that had requested. It is not difficult to imagine the cost of this procedure. In addition, the previously used emitting radionuclides, together with gamma radiation necessary to obtain such images, even useless beta radiation for diagnostic purposes, and much more for radiotoxic tessuti.Il Technetium however, due to its almost ideal radiochemical and its wide availability, ( therefore relatively cost can probably be defined as the best compromise in diagnostic nuclear medicine.

Especially since it only emits gamma radiation of energy is not too high, but enough to get pictures, and because it does not contaminate the environment through the shortness of its half-life (the time in which spontaneously halved its radioactivity) of only 6 hours, which means, for example, that if even a modest amount of radioactivity ever enter the sewer system through urine or feces patients, it is self-exhaustion within a few days.
and "economic" because the generator that produces it provides most of the radioactivity necessary for the operation of a Centre for Nuclear Medicine of medium size, for a whole week, at a cost.
found the ideal radionuclide then became the task of the radio-chemical and radio-pharmacists to identify different substances, linked to technetium, were able to focus in different organs.

many radiopharmaceuticals are now available electively able to concentrate in different tissues and organs, thus allowing the study of their NL Nederlands morpho-functional. They may be "marked" easily and quickly (mostly with the introduction of a solution of Tc-99m into the vial containing the drug itself).

All these features have made the use of Tc-imaging technique called a daily routine in any hospital with a Department of Nuclear Medicine. The

99m Tc, is therefore an "imaging agent" as ideal decade, becoming 99 Tc with a half life of 3.6 hours and by issuing gamma-ray energy of 140 keV. This issue is quite high in energy can easily penetrate the tissue but it is also so low that it can be absorbed with very high efficiency, the crystal of NaI (Tl) detector used as the gamma camera. This therefore allows the visualization of structures inside the body without the risk of exposing the patient to ionizing radiation at high power. Another reason to pay attention to the ^{99m Tc} comes from its characteristic half-life: it is long enough to permit the conduct of subsequent marking operations, administration and biodistribution of the radiopharmaceutical without need to handle excessive amounts of the isotope radioactive compensate for losses due to its decay also makes it possible to conduct accurate analysis of imaging, protraibili for a period of several hours, without having to significantly increase the dose of radiopharmaceutical injected.

important invention that allowed the hospitals to dispose of 99m Tc generator was 99 Mo / 99m Tc, developed over the past 50 years at Brookhaven National Laboratory. Its operation is based on the decay of 99 Mo (E b-max = 1.36 MeV, t _{1 / 2} = 67.0 h) in 99m Tc, which occurs with an efficiency of about 87% , While the second is the reaction product 99 Tc, in which the 99 Mo can also decay directly.

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Nuclear Medicine

The concepts and any information regarding the operating procedures described, handling and use of radiopharmaceuticals, drugs and products present in the late entries have only illustrative and informative and do not allow yourself to acquire the manual skills and experience necessary for their use or their practice.

THE ATOM






Overview:

In contrast to radiological images, which are obtained using the attenuation of the beam of X-rays by the tissues interposed between the equipment that produced them and the system of detection, medical and nuclear images are obtained means of detecting radiation emitted by radiopharmaceuticals distributed in the body. E 'then the patient that emits gamma radiation or X that are recorded by special equipment (gamma-cameras, PET) to recreate the picture. From the term "scintillation", which defines the physical phenomenon exploited by such devices are called the images "scintigraphy.

The various nuclear medicine techniques provide for the administration to patients of a radiopharmaceutical (radionuclide + a molecule), suitably chosen in such a way that focuses on the organ under study or in order to follow over time particular biological function
The distribution of the radiopharmaceutical in the body depends on the chemical and physical constitution of the same, the route of administration, the ability to cross biological barriers, metabolic conditions of the patient.

The scintigraphic images express the spatial-temporal or spatial distribution of the radiopharmaceutical. Information obtained can be expressed in the form of numerical parameters, allowing you to get order data quantitativo.La peculiarities of these images is, therefore, to be "functional", ie the morphological expression of a vital function.

The nuclear medical methods and have had a major role in BIOMEDICA.Di SEARCH particular interest in this regard are the new opportunities provided by positron emission tomography (PET) that can use the same molecules that normally come in tissue metabolism, such as glucose, carbon, oxygen and nitrogen. The use of radionuclide stations
positrons (positive electrons), as Carbon-11, Nitrogen-13, oxygen-15, fluorine-18 can mark the biological molecules by replacing one or more stable isotopes by their radioactive isotope, with the advantage of not changing in any way other physical and chemical characteristics, thus maintaining unchanged the biodistribution and function.

The Nuclear Medicine is a specialized medical discipline that exerts its activity with the purpose of diagnosis and therapy (or research) as the type of unsealed radioactive substance used and the dose of ionizing radiation administered. The dose then administered to the patient and these also becomes a source of radioactivity. The radioactivity is taken up by special external devices to the patient that reproduce the image of the examined organ. There is a fundamental difference, therefore, with radiology, in fact, this patient is crossed by the ionizing radiation produced by external devices to it. Normally, to examine a particular organ or system is necessary to tie ionizing radiation to a chemical called radiopharmaceutical . The higher or lower concentration of the radiopharmaceutical in 'organ or system to be tested shows normal function or altered. Nuclear Medicine provides information so eminently functional of a particular organ or system considered. As opposed to radiology, where the information is mostly morphological. Nuclear Medicine is required the active participation of the body, can be done because the radiograph of a corpse, but not a scan.

Diagnosis
Radiation yo + b for diagnosis, namely the display of anatomical structures and tissues that allows you to highlight any abnormal morphological or functional. A very important example is the issuer of radioisotope gamma 99m Tc is widely used in the most common diagnostic tests, a known positron emitter fluorine-18 instead, artificial radioisotope underlying the operation mechanism of the PET.

Therapy

Radiation b ^- for therapy. An example of particular interest is that of Re-186/188, beta-gamma emitter, if linked to specific antibodies or other substances for receptor activity, it can allow both on-site treatment of tumors that biodistribution studies. Depending on the location of the radiotracer imaging in vivo using, you can also study the genotoxic damage in specific body areas, such as the marrow.
Another possibility for the application of radio-based Re-188 on treatment of rheumatoid arthritis.

Radionuclides

Information diagnostic or therapeutic effect is related use of radionuclides:

1. in chemical form very simple: for example, the cation ²¹⁰ TI ⁺ is retained by the myocardial cells as analogue of potassium and allows you to highlight ischemic phenomena, radioactive isotopes of iodine in the form of iodide, are located in the thyroid and are used as tracers in the synthesis of thyroid hormones.





2. incorporated into compounds more or less complex through a series of special chemical manipulations. This applies to most of the radioactive elements used in Nuclear Medicine. The synthesis techniques used allow to obtain stable and compatible with biological systems in which the body are injected.

The radionuclide used to excellence is the technetium-99m, which emits gamma radiation with energy of 140 keV (optimal for gamma camera ) and has a 'half-life about 6 hours, consistent with the duration of the tests but still short enough to allow irradiation of a limited patient population. The 99mTc is produced through a 99Mo-99mTc generator that ensures optimum availability.

Other gamma-emitting radionuclides are used less often:

• the gallium -67;





• 's Indian -111;





• the iodine -123 and -131 (which also emits beta)





• the thallium -201

Radionuclides beta + channels, to study with the PET method are:

• the fluorine -18





• 's oxygen -15





• ' s nitrogen -13





• the carbon -11

They fell in a relatively very short and need, for their production, a machine called a cyclotron .

The ionizing radiation emitted can be formed by alpha particles (helium nuclei), beta negative particles (electrons) or positive (positrons), or gamma radiation, often a combination of several of these components. This decay occurs according to a general law (of exponential type, statistically random) and I determining the half life or half-life physics, ie the time necessary because the radioactivity contained in a certain amount of radioisotope is reduced to half the initial value.

The half-life (which can vary from a few seconds to several minutes, hours, or many years) is a constant characteristic for each specific radioisotope (which is the distribution emission spectrum for that isotope.) Another fundamental property of radioisotopes is that the chemical reactivity of these elements is identical to that of the corresponding stable elements. The chemical reactivity is characteristic of each element is in fact linked to the outer shape of the orbit e (which determines the value of each chemical element), the isotope that identical (the only change concerns the core) must be to the stable. What distinguishes a radioisotope from the corresponding element is only native is the only nuclear instability and therefore the emission of radioactivity, it is this mission radioactive (or rather its extent from outside the body) which allows the execution of medical examinations nuclear, while biological systems (cells, tissues, organs) are not able to recognize the radioisotope stable as the element other than the native (as is the case for a stable isotope mass).

Therefore, to determine the distribution in the body of a radioactive substance is equivalent to determine the distribution of the corresponding non-radioactive substance. Ionizing radiation of alpha and beta are generally negative taken up almost entirely of biological structures of small thickness (few microns or a few millimeters at most), the radioisotopes that emit primarily this type of ionizing radiation are therefore not generally used for nuclear medical diagnostic applications, which are rule-based detection outside the body of the distribution of radiopharmaceuticals within the living organism. For in vivo diagnostic purposes, is then used radioisotopes that emit gamma radiation of energy mainly suitable for the measurement of them from outside by nuclear medical instruments most commonly used, ie ranges rooms.

Among the gamma-emitting radioisotopes are preferred those with minimal emissions corpuscular alpha or beta, with a potential therapeutic effect is concentrated selectively neoplastic lesions, but which have a load radiobiological not justified in the case of diagnostic applications. In addition, the radioisotopes are preferred range issuers with a short half-life, so that doses can be sufficient to allow detection from the outside with a statistically satisfactory, but without result, while significant radiobiological risks for all patients' diagnostic test.

Radiopharmaceuticals

A fundamental concept that distinguishes the substance administered exams-nuclear (ie, radiopharmaceuticals) than to contrast media used in radiological investigations is that radiopharmaceuticals are administered in absolute terms (ie in terms of mass) is negligible, less often in nanomolar quantities. Collecting them from the outside is in fact based on the attenuation of a beam of X-rays (as in the radiological investigations), but simply on the issue on their part of radiation energy range suitable for the detection of the exterior. The biological systems studied so therefore do not suffer any "disturbance" metabolic, and unwanted side effects associated with administration of radiopharmaceuticals are considered exceptional. Radiopharmaceuticals can be constructed from simple molecular species (such as the radioisotope in the chemical form of sodium iodide), or very complex molecular species (such as immunoglobulin specific for a tumor-associated antigen, or receptor structures recognized by a messenger, etc.).. The radioiodine is probably the example most historically consolidated radioisotope used to prepare different radiopharmaceuticals.

fact, in the simple form of iodide ion (classically in the form of iodine-131 is currently in the atomic form of iodine-123, both are identical in terms of chemical Iodine-127 native this as an essential element in our diet), it is the ideal radiopharmaceuticals to assess morpho-functional body that normally use this element to its processes of hormone synthesis, namely the thyroid gland. However, the radioactive iodine can also be incorporated into more complex molecules such as, for example, ortho-iodoippuranico acid, a substance that normally undergoes a total excretion at the level of glomeruli and renal tubules. This substance is so marked with radioactive iodine and then a radiopharmaceutical that through evaluation of its renal clearance, allows to estimate the effective renal plasma flow. However, radioiodine can be marked even more complex molecules to proteins such as antibodies directed specifically against certain tumor-associated antigens expressed on the surface of tumor cells (allowing you to locate scintigraphically tumor lesions), and so on. The important concept is that the whole body distribution of a given radiopharmaceutical does not depend on the physical characteristics of the radioisotope used for its preparation (such as the physical half-life or the type of radioactive emission), but only on the chemical form of the same radiopharmaceutical. This concept explains why, despite the number of radioisotopes most commonly used for conventional nuclear medicine is relatively limited (ie, technetium-99m, iodine-131, iodine-123, Gallium-67, thallium-201, indium-111, and Xenon-133), the number of conventional radiopharmaceuticals actually available is much higher, ie more than 30.

From a general point of view, the various radiopharmaceuticals in the body behave differently, according to two basic types of distribution. In some cases, the indication provides a diagnostic radiopharmaceutical accumulating in high concentration in a diseased tissue, such as the aforementioned labeled antibody which accumulates in tumor lesions that express on their surface antigen tumor-associated dall'anticorpo recognized that represents the behavior of radiopharmaceuticals within the category of so-called "positive indicators" (the disease process is therefore scintigraphically identified as "hot area"). Some radiopharmaceuticals accumulate, however, physiologically normofunzionanti tissues, so the diagnostic indication is provided by their absent tank (or reservoir) in the portion of the body where healthy tissue is replaced by abnormal tissue, the example already cited that the radiopharmaceutical does not display an area of \u200b\u200bventricular myocardium (for perfusion defect caused by significant coronary stenosis) represents the behavior of radiopharmaceuticals within the category of so she called "negative indicators" (the disease process is identified as a "cold area").

radiolabelled These are then called radiopharmaceuticals and, currently, according to Legislative Decree n.178 of 29/05/1991, are classified as medicinal products.

It is, in general, compounds labeled with radioactive isotopes for use in nuclear medicine and therefore prepared in a form suitable for use in vivo (in accordance with the regulations of the official pharmacopoeia). A radiopharmaceutical is thus characterized not only by the chemical structure and pharmaceutical form, which is also marked by the radionuclide, whose properties depend on not only the possibility of synthesis of the radiopharmaceutical and its stability, but also the efficiency of detection and radioesposizione to the patient.
Therefore, the ideal characteristics of a radionuclide for use in the preparation of a radiopharmaceutical can be considered as follows:

• monoenergetic emission of sun radiation energy range between 100 and 200 keV;





• short half-life;



• transformation into a stable nuclide;



• high activity specification;



• high purity radionuclides,



• readily available;



• low manufacturing cost,





• chemical properties that allow you to easily bind to molecules of biological interest.
  

Historically, the first radiopharmaceutical introduced into clinical practice was iodine-131 (131 I), used in the study of thyroid diseases. They were then gradually developed other radiopharmaceuticals, such as 131 I, however, had physical and radio-biological-optimal. This obligation to employ very small amounts, which could be obtained only poor images, or preclude entirely the possibility of obtaining them. The decisive impetus to the growth of nuclear medicine, which has helped the transformation from a branch of radiology self-discipline, came from the design of the first generator 99mTecnezio, built on the "Brookhaven Laboratory in New York in 1958 and introduced the use clinician in 1963.

Of all the proposed radionuclides, in fact, the Technetium-99m is what has properties more like those above, although, being a transition metal, and, moreover, not present in nature, does not come easily be part of the structure of biological molecules. Nevertheless, thanks to the knowledge on its chemical properties are ideal, today is by far the most used radionuclide in clinical practice.

Radiopharmaceuticals are administered directly to the patient, orally or intravenously.
These doses do not cause damage because the doses used are low and the radioisotopes used have very low toxicity and energy. In addition, nuclides have lifetimes media rather small and are generally present in the radiopharmaceutical inactive number of atoms that decrease the specific activity of the product (radioactivity per unit mass of the element, usually expressed in MBq or GBq / g).

The localization of the radiopharmaceutical after treatment in the patients with the information or the therapeutic effect derived from them are determined by the characteristics of the radiopharmaceutical as a whole:

• Physical and chemical characteristics: type emission of the radioisotope, charge, lipophilicity, size of the radioactive complex.



• Possible interactions with components biological (blood tissue, cells, membranes, enzymes, receptors).

Radionuclides used in nuclear medicine are produced artificially by

Accelaretori of charged particles :

• Cyclotrons

Nuclear reactors

• with processes of neutron capture (n, gamma): 98 Mo (n, gamma) -> ⁹⁹ Mo




• with fission (n, fission): 235 U (n, fission) -> ⁹⁹ Mo

Generators

The following table lists some of the main radioisotopes used in nuclear medicine and their applications prevalent:

radioisotope	use
Technetium 99m	in vivo. It is used for skeletal scintigraphy, liver, kidney, brain, thyroid, liver function. Half-life: 6 hours.
Fluoro 18	in vivo. Used for displaying scintigraphy in oncology, cardiology (cardiac metabolism, coronary blood flow, etc..) And neurological (Alzheimer's diagnosis, epilepsy, traumatic brain injury, etc.).. Half time: 110 min.
Rhenium 188	in vivo. Used as a therapeutic agent in the treatment of cancer and arthritis and as a tracer is similar to 99m Tc. Half-life: 17 hours.
Cobalt 60	in vivo. Used in radiotherapy for cancer. Half-life: 5 years.
Iodine 131	in vivo. Used for diagnosis and treatment of thyroid cancer thyroid, renography and the so-called investigation totalbody . Half-life: 8 days.
Thallium 201	in vivo. Need for myocardial scintigraphy. Half-life: 3 days.
Iodine 125	in vitro. Handles all the analysis of radioimmunoassay for the determination of thyroid hormones. Half-life: 60 days.

Preservatives In Chapstick

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"Any path is only a street, and there is no affront, to oneself or others, in dropping, if that is what your heart tells you to do ... Examine each street carefully and thoughtfully. Try it as many times as you think necessary. So ask yourself, and yourself alone, one question ... This street has a heart? If it did, the way is good. If you do not have it, is useless. "
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