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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: