FR2628428A1 - Radiophaermaceutical technetium and rhenium-nitrogen cpd. complexes - Google Patents

Abstract

Nitro complexes of radioactive metals are prepared as follows, an oxygenated cpd of a metal M, where M is 99mTc, 186Re, or 188Re, is reacted with a first ligand (I) which is an aliphatic or aromatic phosphine or polyphosphine, which may be substituted and a second ligand (II) which may be an ammonium or pharmaceutically-acceptable metal nitride, a compound having a group -(-)N-N(-)- each N atom being attached to H or monovalent organic groups through carbon atoms, or one N may be attached to a bivalent C atom through a double bond. (I) and (II) are generally used as alcoholic or aqueous alcoholic solutions, and these are added to a solution of sodium pertechnate or perrhenate. (I) may be a phosphine of formula R1P(R2)R3 or a polyphosphine of formula (A) or (B) where R1 and R2 are H, alkyl, aryl, alkoxy, or substd alkyl or aryl. Typical ligands are triphenyl phosphine, triethyl, phosphine, diethyl phenyl phosphine, and tris (2-cyanoethyl)phosphine. Suitable ligands (II) include S-methyl-beta- N(2-hydroxyphenyl) methylene dithiocarbazate, S-methyl dithiocarbazate, S-methyl N-methyl dithio carbazate, alpha-N-methyl S-methyl-beta-N-pyridyl methylene dithiocarbazate, S-methyl-beta-N-(2,5-dihydroxyphenyl) methylene dithiocarbazate, alpha-N-methyl-S-methyl-beta-N(2-hydroxyphenyl) methylene dithiocarbazate, hydrazine, semicarbazide, thiosemicarbazide, 1-methyl-3-thiosemicarbazide, 4-methyl-3-thiosemicarbaz ide, amino acetone semicarbazone, carbohydrazide, thiocarbonnydrazide, acethydrazide, methyl hydrazine carboxylate, 2-furoyl hydrazide, salicycoyl hydrazide, amino guanidine and sodium azide.

Description

PROCESS FOR THE PREPARATION OF TRANSITION METAL COMPLEXES
USEFUL AS RADIOPHARMACEUTICAL PRODUCTS OR FOR THE
SYNTHESIS OF NEW RADIOPHARMACEUTICAL PRODUCTS
DESCRIPTION
The subject of the present invention is a process for the preparation of transition metal complexes, which can be used in particular as radiopharmaceutical products or for the synthesis of new radiopharmaceutical products.

 More specifically, it relates to the preparation of nitrido complexes of transition metals having a portion MN, wherein M represents a transition metal.

 It is specified that a transition metal is a metal whose layer d is partially filled in the usual oxidation state of this metal. These are the elements that complete Periods III to XII of the periodic table of 18-column items.

By way of example of such metals, mention may be made of Tc, Ru,
Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta.

 In particular, the invention relates to the preparation of radioactive transition metal complexes useful as radiopharmaceuticals for diagnosis or therapy.

 Among the compounds that can be used for diagnosis, mention may in particular be made of technetium 99-m complexes. The complexes that can be used for therapy can be, for example, rhenium complexes.

 The four radiopharmaceuticals using radionuclide Tc are compounds frequently used in nuclear medicine for diagnosis because of the physical and chemical characteristics of this radionuclide.

 Indeed, it gives only a gamma emission, has optimal gamma energy for external detection (140 Kev) and a short physical half-life (6, O2h), which allows to deliver a low dose irradiation to the patient. In addition, the cost of this radioelement is low and is commercially available. Finally, the richness of technetium chemistry makes it possible to obtain a wide variety of radiopharmaceutical products.

The source of this radionuclide is the 99mMo 99m generator
Tc which generally provides an aqueous solution of NaCl, 0.154 M pure or containing stabilizers, in which
99m 99 - the pertechnetate ion (TcO + TcO4) is present at total concentrations ranging from 10-7 to 10-9 mol / l.

Generally, this radionuclide is used in the form of complexes. These are formed by reduction of the pertechnetate ion by means of reducing agents such as ferrous ions, stannous ions etc., and reaction of the reduced technetium with appropriate ligands. The complex can also be formed by a ligand exchange reaction on a preformed Labile complex of technetium, for example by ligand exchange on the complex.
Tc-Sn pyrophosphate, Tc-Sn glucoheptonate, Tc-Sn tartrate, as described by E. Deutsh et al in Progr. Inorg. Chem.

(Australia), vol. 30, pp.75-139 (1983).

When a process comprising a reduction step is used for the preparation of these technetium complexes, the complex formed corresponds to the +5 or +4 oxidation states of the technetium and may also correspond to lower oxidation states such as +3 and +1. Dance in the case of Tc (V) complexes,
+ we can have a part oxo (TcO) or transdioxo (TcO)
2
We also know a process for the preparation of complex
2+ of technetium having a portion (TcN), which is described by
J. Baldas et al. in J. Chem. Soc. Dalton Trans. 1981, pp.

1798-1801; in Int. J. Appl. Radiat. Isot. 36 (1985), pp.133139 and in International Patent Application i085 / 03063.

 Complexes of this type are of interest because they are very stable to hydrolysis and can be used without modification of the Tc = N portion for substitution reactions with other ligands, resulting in a wide variety of complexes. of technetium.

The process currently known for preparing such complexes consists in reacting a pertechnetate such as sodium pertechnetate with sodium azide and a halogenated hydric acid such as hydrochloric acid, in order to obtain
+ intermediate product of formula R (TcNX) in which R
4 is a cation, for example sodium, ammonium or other alkali metal, and X is a halogen such as chlorine or bromine.

To carry out this reaction, a solution of sodium pertechnetate (Tc-99m) is evaporated to dryness using a rotary evaporator, and the dry residue is then added with sodium azide and concentrated hydrochloric acid. Refluxed for about 5 minutes to complete the reduction and destroy the excess azide and evaporated again to dryness using a rotary evaporator. This gives a residue containing the
+ 99m compound R (Tc> NCl) which is the intermediate product from
4 of which can be formed by reaction with appropriate ligands, technetium complexes usable as radiopharmaceuticals.

 This method is difficult to apply to the manufacture of kits for medical use because it is long and comprises at least three stages in which is used twice a rotary evaporator, which is not easy to implement in a hospital service of nedicine nuclear. In addition, this method is difficult to use for the manufacture of kits for medical use because the sterility and the apyrogeneity of the solutions are difficult to control throughout the operations. Therefore, the product finally obtained must be sterilized after labeling with Tc-99m, either by passing on a sterilizing membrane, or by heat sterilization, and it must undergo a control of absence of pyrogen before the injection on the man.

 In the case of the preparation of complexes usable for therapy, it is important to use a method of preparation leading to a high yield of the desired products.

In the case of the product developed by Baldas or
Griffith (Coord Chem Rev 8, 1972, pp.369-396) for the preparation of nitrido complexes of technetium, high yields of complexes can not be obtained.

 It is the same with the methods generally used to prepare rhenium complexes.

 The present invention specifically relates to a process for preparing transition metal complexes such as technetium and rhenium, which; overcomes the disadvantages described above.

The process according to the invention for the preparation of a product comprising a nitrido complex of a transition metal comprising a part M ~ N with M representing the transition metal, is characterized in that an oxygenated compound is reacted with transition metal M with a first ligand chosen from the group of aliphatic and aromatic phosphines and polyphosphines, and a second nitrogen ligand comprising an ON-Nv unit in which the Ns are connected to hydrogen atoms and / or organic groups monovalent via a carbon atom or in which one of the N is connected to the carbon atom of a divalent organic group via a double bond and the other N is connected to hydrogen atoms and / or monovalent organic groups by
The intermediate of a carbon atom.

 According to this method, a nitrido complex of a transition metal can easily be obtained because it is sufficient to mix the reagents described above to form the nitrido complex.

 Generally, the first and second ligands are used in the form of alcoholic or aqueous-alcoholic solutions, and by simple addition of these solutions to the oxygenated compound of the transition metal, for example to sodium pertechnetate or sodium perrhenate, there is obtained directly a product containing the desired nitrido complex.

 Thus, in this case, it is not necessary to first perform dry evaporation steps of the reagents. Nor is it necessary to sterilize the product obtained at the end of the reaction because it is sufficient to use a sterile solution of the oxygenated compound of the transition metal.

 In addition, the process of the invention makes it possible to obtain high yields, which was not the case with the processes of the prior art.

The oxygenated transition metal compounds M used in the invention are salts of the type MO M ', with M'
4 representing an alkali metal or ammonium.

 In the process of the invention, the first phosphine ligand acts as a reducing agent for the transition metal and promotes the formation of the M = N core as well as the quantitative binding of the second nitrogen ligand. Indeed, in the absence of the first ligand, it is impossible to obtain by reaction of the second ligand with the oxygen compound of the transition metal complex having a part MEN.

 To carry out the reaction, the second nitrogen ligand and the phosphine can be aseptically introduced into a container, and then the required amount of oxygenated transition metal compound, for example technetium 99n pertechnetate, can be added after adjusting the pH to an appropriate value. by addition of acid or base. The reaction can then be carried out at room temperature or at a higher temperature of from 50 to 1000 ° C. The temperature and the pH used depend in particular on the second nitrogen ligand. Generally one operates at pH lower than 4.

 The product obtained by this process can be used as such as a radiopharmaceutical for therapy or diagnosis.

It can also be used as an intermediate for the manufacture of other nitrido complexes that can be used as radiopharmaceuticals for diagnosis or therapy. In this case, the ligands of the nitrido complex of technetium obtained previously with a third organic ligand are exchanged.
nucleophilic group having, for example, a better tropism for certain organs of the human body or else a monoclonal antibody or an antibody fragment.

 This exchange reaction can be carried out simultaneously during the formation of the nitrido complex by reacting together the oxygenated compound of the transition metal, the first ligand, the second nitrogen ligand and the third organic ligand containing a nucleophilic group, the monoclonal antibody or the antibody fragment. This reaction may also be carried out in two stages, ie a first stage in which the oxygenated compound of the transition metal is reacted with the first and second ligands, and then a second stage in which the product obtained is reacted as a result of the first step with the third ligand, the monoclonal antibody or the antibody fragment.

 The nucleophilic organic ligands used for this exchange reaction can be very diverse.

By way of example, it is possible to use amines, thiols, thioethers, oximes, phosphines and polyfunctional ligands of the polyaminopolythiol type.

 When the reaction is carried out with a monoclonal antibody or an antibody fragment, a transition metal-labeled antibody can be prepared in this way.

 The antibody or labeled antibody fragment obtained is very interesting, for example for the detection of tumors.

Indeed, after reaction with the transition metal complex, the monoclonal antibody or the antibody fragment is bound to the transition element such as technetium 99m, but it can react with the corresponding antigens. Thus, the specificity of the antibody is maintained and the labeled antibody is stable.

Also, this labeled antibody can be used for the detection of tumors as it will naturally go to the corresponding antigen and allow the visualization of the tumors.

 In the process of the invention, the choice of ligands used is important because it conditions the properties of the product obtained.

 The first ligand which makes it possible to obtain the formation of a nitrido complex is an organic electron donor phosphor ligand chosen from aliphatic and aromatic phosphines and polyphosphines.

peuvent être identiques ou différents, représentent un atome d'hydrogène, un radical alkyle, un radical aryle, un radical alcoxy ou un radical alkyle ou aryle substitué par un groupement choisi parmi les radicaux amino ou amido.Usable phosphines can meet the formula
1 2 in which R, R and

may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical or an alkyl or aryl radical substituted with a group chosen from amino or amido radicals.

 Examples of phosphines of this type include triphenylphosphine, diethylphenylphosphine, triethylphosphine and trimethylphosphine. Generally, it is preferred to use triarylphosphines such as triphenylphosphine, because they are less oxidizable than trialkylphosphines.

Polyphosphines that can be used in
The invention can respond to the formulas:

 In which R and R, which may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical or an alkyl or aryl radical substituted with. a group selected from amino and amido radicals, and m is an integer ranging from 1 to 4.

 As examples of such polyphosphines, mention may be made of bis (dimethyl-1,2-phosphino) ethane and bis (diphenyl-1,2-phosphino) ethane.

As has been seen previously, the second ligand is a nitrogen compound comprising the unit

456 7 dans laquelle R , R , R et R qui peuvent être identiques ou différents, représentent un atome d'hydrogène ; un radical alkyle ; un radical aryle ; un radical alcoxy ; un radical alkyle substitué par au moins un groupement choisi parmi les radicaux hydroxy, carboxy, amino, amido et mercapto ; un radical aryle substitué par au moins un groupement choisi parmi Les atomes d'halogène et les radicaux alcoxy, hydroxy, amino, mercapto et amino substitué par au moins un radical alkyle ; un radical répondant aux formules

Nitrogen compounds of this type can meet the formula:

Wherein R, R, R and R, which may be the same or different, represent a hydrogen atom; an alkyl radical; an aryl radical; an alkoxy radical; an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals; an aryl radical substituted with at least one group selected from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical; a radical corresponding to the formulas

Wherein R and R, which may be the same or different, represent a hydrogen atom, an alkyl radical, or an amino radical; a radical of formula:

Wherein R represents a hydrogen atom, an alkyl radical or an aryl radical; a radical of formula R -CO- with II
R representing an alkyl radical, an alkoxy radical, an aryl radical which is unsubstituted or substituted by at least one group chosen from halogen atoms and hydroxyl radicals, or a radical derived from a heterocycle which is unsubstituted or substituted by at least one group chosen from halogen atoms and
Hydroxy groups; or in which R and R may together form a divalent radical of the formula:

Wherein R represents -CH2-NH2, an aryl radical unsubstituted or substituted by at least one group selected from halogen atoms and hydroxy, alkoxy, amino, mercapto and amino radicals substituted by at least one alkyl radical, or a radical derived from a heterocycle which is unsubstituted or substituted by one or more groups chosen from halogen atoms and hydroxyl, alkoxy, amino, mercaio and amino radicals substituted by at least one alkyl radical and R represents an atom of hydrogen, an alkyl radical or an alkyl radical substituted with at least one group chosen from hydroxyl radicals,
Carboxy, amino, amido and mercapto; and R and R have the meaning given above.

These nitrogen compounds may belong in particular: to the group of hydrazine and its derivatives, for example
alkylhydrazines, semicarbazides, hydrazides,
thiosemicarbazides, Carbohydrazides,
thiocarbohydrazides, acethydrazide, hydrazinecarboxylates
and aminoguanidines, to the group of dithiocarbazic acid and its derivatives, and to the group of products obtained by condensation of the compounds
described above with ketones or aldehydes
aliphatic or aromatic.

Thus, the second nitrogen ligand may be dithiocarbazic acid or a derivative thereof having the formula

In which R represents a hydrogen atom, a radical
Alkyl or an aryl radical, and R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals; or an aryl radical substituted with at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical.

It can also be a condensation product obtained by reaction of dithiocarbazic acid with a ketone
Or an aliphatic aldehyde of the formula R -CO-R. In this case, he answers the formula:

Wherein R represents a hydrogen atom, an alkyl radical or an aryl radical; R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted by at least one group chosen from hydroxy, carboxy, amino, amido and mercapto radicals, or an aryl radical substituted by at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical; and
R and R, which may be identical or different, represent a hydrogen atom, an alkyl radical or an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, ami and mercapto radicals.

The dithiocarbazic acid derivative used as the second ligand may also be the condensation product of dithiocarbazic acid with a ketone or an aromatic aldehyde. In this case, the derivative responds to the formula:

10
wherein R represents a hydrogen atom, an alkyl radical or an aryl radical; R represents a hydrogen atom,
an alkyl radical, an aryl radical, an alkoxy radical, a
alkyl radical substituted by at least one group chosen from
hydroxy, carboxy, amino, amido and mercapto radicals or a
aryl radical substituted by at least one group selected from
the halogen atoms and the alkoxy, hydroxy, amino mercapto and amino radicals substituted by at least one alkyl radical;
represents a hydrogen atom, an alkyl radical, a radical
allyl substituted with at least one group selected from leâ
hydroxy, carboxy, amino, amido and mercapto radicals, R 'represents a hydrogen atom, a halogen atom, a radical
alkoxy, an amino radical, or an amino radical substituted by at least one alkyl group, R represents a hydrogen atom,
a hydroxy radical or a mercapto radical, E represents an atom
of carbon or a nitrogen atom, and n is an integer ranging from
18 from there 4, where n is 2 and both R's are adjacent and together form an aromatic ring.

It is also possible to use as second ligand the
product obtained by condensation of dithiocarbazic acid with a ketone having a 5-membered heterocycle. In this case, the second ligand corresponds to the formula:

Wherein R represents a hydrogen atom, an alkyl radical or an aryl radical; R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals, or an aryl radical substituted with a group chosen from halogen atoms and alkoxy, hydroxy, amine mercapto and amino radicals substituted by at least one alkyl radical; R represents a hydrogen atom, an alkyl radical or an alkyl radical substituted with at least one group chosen from
18 hydroxy, carboxy, amino, amido and mercapto radicals, R represents a hydrogen atom, a halogen atom, an alkoxy radical, an amino radical, or an amino radical substituted by at least one alkyl group, G is S or O, and p is 1, 2 or 3.

The second ligand may also be hydrazine or a hydrazine derivative corresponding to the formula:
20 21
R -NH-NH-R
Wherein R is a hydrogen atom or an alkyl radical
And R is a hydrogen atom or a radical selected from radicals of formula:

 In which R and R, which may be the same or different, represent a hydrogen atom, an alkyl radical or an amino radical, R represents an alkyl radical and R represents an aryl radical which is unsubstituted or substituted by at least one chosen group. among the halogen atoms and the hydroxyl radicals or a radical derived from a heterocycle which is unsubstituted or substituted by at least one group chosen from halogen atoms and hydroxyl radicals.

 The alkyl and alkoxy radicals used in the ligands described above may be linear or branched radicals; they generally have 1 to 3 carbon atoms.

 Aryl radicals are radicals derived from a ring by removal of a hydrogen atom such as phenyl and naphthyl radicals. By way of example, radicals derived from heterocyclic rings may be furfuryl, pyridyl or thiofurfuryl radicals.

 The ligands described above are commercial products or can be prepared by conventional methods.

 In the process of the invention, where technetium or rhenium is used as the transition metal, the nitrogen ligands used may be monodentate, bidentate or tridentate.

dans laquelle A représente le ligand à base de phosphine et B, C et D représentent le ou les Ligands azotés..Indeed, it seems that the nitrido complex obtained
The following basic square pyramid structure in the case of
Tc:

in which A represents the ligand based on phosphine and B, C and D represent the nitrogen ligand or Ligands.

la position B est occupée par l'un des atomes d'azote du dithiocarbazate alors que les positions C et D sont occupées par les atomes O et S- du dithiocarbazate ionis. Le complexe a ainsi la structure suivante :

In the case of a tridentate nitrogen ligand, such as S-methyl-beta-N (2-hydroxyphenyl) methylenedithiocarbazate of the formula

the position B is occupied by one of the nitrogen atoms of the dithiocarbazate whereas the positions C and D are occupied by the O and S- atoms of the dithiocarbazate ionis. The complex thus has the following structure:

 Thus, if a Tridentate Nitrogen Ligand is used, a single complex will be obtained. In contrast, when using monodentate nitrogen ligands, there can be different types of complexes depending on whether the first phosphine ligand occupies one or more of the A, B, C and D positions of the complex.

 When the complex obtained from the first and second ligands is reacted with a third nucleophilic organic ligand, it is necessary for this third organic ligand to be monodentate, bidentate or tetradentate in the case where the transition metal is Tc. Indeed, in this case, it is possible to obtain the replacement of the first and second ligands by the third tetradentate ligand. In the case of mono or bidentate ligands, several complexes can be prepared, but it is observed that there is generally a rearrangement of the complexes obtained in favor of the technetium complex comprising mainly the third ligand.

In the invention, the choice of ligands used is of great importance because it conditions in particular the properties of the complex obtained. Indeed, by choosing a second nitrogen ligand having a particular affinity for certain organs and using a radioactive transition metal such as
Tc-99m, suitable for scintigraphic examinations, the method of the invention can be used to prepare a radiopharmaceutical composition directly usable for diagnosis.

 In this case, it is of course also necessary that the first and second ligands are not toxic and can be administered to humans.

Also, the subject of the invention is also a kit for the preparation of a nitrido complex of radioactive transition metal, in particular technetium, which comprises: a first bottle containing the first phosphine ligand
and a second vial containing the second nitrogen ligand.

 Thus, it is possible to prepare directly from this kit the desired radiopharmaceutical product, in a nuclear medicine hospital department, by mixing the contents of the two fLacons and adding, for example, a solution of alkali metal or ammonium pertechnetate. The first and second ligands may be present in the first and second bottles respectively in liquid form or in lyophilic form.

 In some cases, the first and second ligands can also be mixed in the first vial and the solution of the oxygenated transition metal compound, for example pertechnetate or perrhenate, can be added at the last minute to prepare the radiopharmaceutical.

 As previously discussed, the transition metal complex obtained from the first and second ligands can also be used as an intermediate product for the preparation of another transition metal nitrido complex by exchange reaction with a third ligand, a monoclonal antibody or an antibody fragment.

 The product obtained as a result of this reaction can also be used as such as a radiopharmaceutical for either diagnosis or therapy. In this case, the kit for the preparation of the radiopharmaceutical may comprise a third vial containing the third nucleophilic organic ligand, the monoclonal antibody or the antibody fragment.

 Other features and advantages of the invention will appear better on reading the following examples given of course by way of illustration and not limitation.

EXAMPLE 1
In a penicillin-type flask, 0.4 ml is introduced.
-2 of a solution containing 2.10 mol / l (2.5 mg / ml) of S methyldithiocarbazate (second ligand) 2 in ethyl alcohol, then 0.2 ml of a solution at 2.10 mol / l (Smg / ml ) of triphenylphosphine (first ligand) in ethyl alcohol, and 0.1 ml of 1N hydrochloric acid. 0.5 to 1 ml of sodium pertechnetate solution (Tc-99m) is then added and the reaction is carried out at 800 ° C. for 30 minutes.

 The thin layer chromatographic analysis of the product obtained shows that it is a nitrido complex of technetium comprising the TcN core.

EXAMPLES 2 to 13
The same procedure as in Example 1 is followed to prepare from the ligands given in Table 1 which follows, nitrido complexes of technetium by introducing into the
5.10 to 1.10 mmol of the second ligand, 4 mmol of the first ligand and 0.1 ml of 1N HCl, and then 0.5 to 1 ml of sodium pertechnetate solution are added.

 The chromatographic analysis of the products obtained shows that they are indeed nitrido complexes comprising the Tc N.

EXAMPLE 14 ~
In a penicillin-type flask, 0.4 ml of an alcoholic solution of the dry ligand, consisting of a solution containing 2.5 mg / ml (1.5 × 10 mmol / l) of S-methyl-beta-N (2 × (hydroxyphenyl) methylene dithiocarbazate in ethyl alcohol, 0.2 ml of a 5 mg / l solution (2.10 mmol / l) of triphenylphosphine (first ligand) in ethyl alcohol, and 0.1 ml of a solution of 1N hydrochloric acid.

 0.5 ml of a sterile solution of sodium pertechnetate (technetium-99m) corresponding to a radioactivity ranging from 1.8 M Bq to 3.7 6 Bq (0.5 to 100 mCi) is then added, and the flask is heated. at 800C for 30 minutes.

 Whatman KC 18 reversed phase thin layer chromatographic analysis using a mixture of methanol, acetonitrile, tetrahydrofuran and 0.5M ammonium acetate (proportions 3: 3: 2: 2) as the solvent shows the appearance of a pure product having an Rf of 0.35, and confirms the presence of the Tc # N moiety.

EXAMPLES 15 to 21
The procedure of Example 14 is repeated with the first and second ligands of Table 2 by introducing into the flask 1.10 to 5.10 mmol of the second ligand, 4.10 mmol of the first ligand and 0.1 ml of 1N HCl, and then adding 0.5 to 1 ml of sodium pertechnetate solution Tc-99m.

 At the end of the operation, the product obtained is subjected to thin-layer chromatography and the mixture is Tc = -N and the phosphine is an integral part of the complex obtained.

EXAMPLE 22
The same procedure as in Example 1 is followed, but using the second Ligand 1-methyl-3-thiosemicarbazide formula

 It is then verified by chromatographic analysis that the complex obtained is indeed a nitrido complex of technetium and that it comprises triphenylphosphine.

EXAMPLE 23
In this example, the same procedure is followed as in Example 14 but using as the second ligand the aminoacetone-semicarbazone of formula:

 It is then verified by thin layer chromatography that the complex obtained is indeed a nitrido complex of technetium.

EXAMPLE 24
In this example, it is introduced in a typical bottle
-3 penicillin ImI of a solution at 5.10 mmol / l of alpha-N-methyl S-methyl-beta-N (2-hydroxyphenyl) methylene dithiocarbate in ethyl alcohol, 0.2 ml of a solution at 6.10 mmol / 1 bis (dimethyl-1,2-phosphino) ethane of formula
(CH) P - CH - CH - P (CH)
32 2 2 32 and 0, 1 ml of 1N hydrochloric acid. 0.5 ml of a sterile solution of sodium pertechnetate (Tc-99m) is then added and the flask is heated at 800 ° C. for 30 minutes.

 A nitrido complex of technetium comprising the first ligand based on di phosphine is thus obtained.

EXAMPLE 25
The same procedure as in Example 24 is followed but using a solution of 5.10 amol / l of bis (diphenyl1,2-phosphino) ethane and a solution of 5.10 mmol / l of alpha-N methyl S-methyl-beta -N (2-hydroxyphenyl) methylenedithiocarbazate.

 A nitrido complex of technetium containing the diphosphine ligand is also obtained.

EXAMPLE 26
In this example, a rhenium complex is prepared by introducing into a penicillin-type vial 7 gnoles of triphenylphosphine and 2 mmol of 2-methyl-beta-n (2-hydroxyphenyl) methylenedithiocarbazate in alcoholic solution and 5 mmoles of acid. hydrochloric acid 1N. Sodium perrhenate is then introduced and the reaction is carried out at 4 ° C.OC for 30 minutes.

 A nitrido complex of rhenium is thus obtained with a yield greater than 90 ×.

 In the following examples, the nitrido complexes of technetium obtained in the previous examples are used to form other technetium complexes that can be used as diagnostic products.

EXAMPLE 27
In this example, the product obtained in Example 14 is used to prepare another technetium complex with a third ligand consisting of N, N'-bis (2-methylpropane-2-thiol) ethane of formula:

 To the contents of the fLacon obtained in Example 14, 0.2 ml of a solution of 4.10 mol / l of N, N'-bis (2-methylpropane-2-thiol) ethane in ethanol is added.

 The pH is brought to 9.5 by the addition of 0.5 ml of a 0.5M carbonate / bicarbonate buffer solution and the flask is heated at 80 ° C. for 30 minutes.

 The resulting product was subjected to thin layer chromatography using silica gel and ethanol-chloroform-benzene solvent (2: 2: 1). The locations of the chromatographic spots correspond to a technetium nitrido complex comprising the TctN part.

COMPARATIVE EXAMPLE I
In this example, a solution of N, N'bis (2-methylpropane-2-thiol) ethane is reacted with sodium pertechnetate (Tc-99m) in the presence of stannous chloride. A diaminodithiolute oxotechnetium is thus obtained which is analyzed by thin layer chromatography under the same conditions as the product obtained in Example 27.

The location of the chromatographic spots for this
3+ Tc complex containing the core (TcO) is different from that obtained in Example 26 with the nitrido complex.

EXAMPLES 28 to 35
The same procedure as in Example 27 is followed to prepare other nitrido complexes of technetium from the products obtained in Examples 1, 2 and 16 to 21 using N, N'-bis (2) as the third ligand. -méthylpropane-2thiol) ethane.

 In all cases, a nitrido complex of technetium containing this third ligand is obtained.

EXAMPLE 36
The same procedure as in Example 27 is followed to prepare a new technetium complex from the product obtained in Example 1 but using as a third
-2 ligand a 6.10 mol / l solution of tetraazaundecane of formula:

 A new nitrido complex of technetium containing tetraazaundecane as ligand is thus obtained.

 The purity of the product is tested by thin layer chromatography using cellulose and a solvent based on ethanol-0.15M ammonium acetate (4: 3 ratio).

EXAMPLES 37 to 44
In these examples, the same procedure as in Example 36 is followed by adding to the product obtained in Examples 2, 14 and 16 to 21, 0.2 ml of a 6.10-2 mol / l solution of tetraazaundecane.

 In all cases, a nitrido complex of technetium containing the tetraazaundecane ligand is obtained.

EXAMPLE 45
To the contents of the flask obtained in Example 16, 0.1 ml of a solution of 6.10-2 mol / l (9 mg / ml) of bis (1,2-dimethylphosphine) ethane dihydrochloride (DMPE) is added. The pH is brought to 10 by the addition of 0, Sml of a 0.5 mol / l solution of bicarbonate / carbonate and the reaction is carried out at 800 ° C. for 30 minutes.

 The product obtained is analyzed by thin layer chromatography (cellulose, solvent: ethanol-O, 15M ammonium acetate, 4: 3). It is thus found that it is a nitrido complex of technetium comprising the third ligand.

In fact, the chromatographic spots obtained with this complex are different from those obtained with the known complexes of technetium having the formula

<tb># 99mTcCl2DMPE2 # + <SEP>
<tb> and

<tb># 99mTcO2DMPE2 #.
<Tb>

TABLE 1

<tb> He <SEP>
<tb> It <SEP> / R <SEP> I
<tb> I <SEP> l <SEP> I <SEP> 2nd <SEP> ligand <SEP> of <SEP> formula <SEP> H2N-N <SEP> 5 <SEP>
<tb> I <SEP> EX <SEP> I <SEP> 1st <SEP> ligand <SEP> | <SEP> I <SEP> R
<tb><SEP> -3 <SEP> -2
<tb> l <SEP> ,,,,, ~~~~~~~~~~~~ ----------------------- <SEP><SEP><SEP> (5.10 <SEP> å <SEP> 1.10 <SEP> mmol / l)
<tb> It <SEP> I <SEP> 141 <SEP> 5
<tb><SEP> 5
<tb> I <SEP> I <SEP> I <SEP> NAME <SEP> I <SEP> R <SEP> I <SEP> R <SEP> I
<tb> I <SEP> I <SEP> I <SEP> i <SEP> I <SEP> I
<tb> I <SEP> I <SEP> triphenyl <SEP> j <SEP> S-methyl <SEP> dithio <SEP> l <SEP> I <SEP> // S <SEP> I
<tb> I <SEP> 1 <SEP> 1 <SEP> | <SEP> phosphine <SEP><SEP> carbazate <SEP> I <SEP> H <SEP> I <SEP> - <SEP> C
<tb> I <SEP> I <SEP> I <SEP> I <SEP> SCH <SEP> j
<tb> It <SEP> I <SEP> I <SEP> 3
<tb> I <SEP> I <SEP><SEP> S-methyl <SEP> N-methyl <SEP> I <SEP> I <SEP> S <SEP> I
<tb><SEP> 2 <SEP> I <SEP>"<SEP> I <SEP> dithiocarbazate <SEP><SEP> CH3 <SEP> 1 <SEP> - <SEP> C
<tb> I <SEP> I <SEP> I <SEP> I <SEP> SCH <SEP> j
<tb> It <SEP> I <SEP> I <SEP> 3
<tb> I <SEP> I <SEP> j <SEP> hydrazine <SEP> under <SEP> form <SEP> l <SEP> lI
<tb> | <SEP> 3 <SEP>"<SEP>"<SEP> | <SEP> me <SEP> of <SEP> dichlorhydra-d <SEP> H <SEP> d <SEP> H <SEP> | <SEP> H
## EQU1 ##
<tb> It <SEP> I <SEP> I
<tb> I <SEP> I <SEP> I <SEP> semi-carbazide <SEP> under <SEP> j <SEP> I
<tb> I <SEP> I <SEP> j <SEP> form <SEP> of <SEP> chlorhy- <SEP> | <SEP> | <SEP> j <SEP> HERE <SEP> - <SEP> NH <SEP> l
<tb><SEP> Z
<tb> 4 <SEP> 4 <SEP> | <SEP> drate <SEP> | <SEP> HH <SEP> 0 <SEP> l <SEP> I
## STR1 ##
<tb> II <SEP> I <SEP> 0 <SEP> I <SEP> I <SEP> I
<tb> It <SEP> I <SEP> I <SEP> I
<tb> 1 <SEP> 5 <SEP> 1 <SEP>"<SEP> I <SEP> Thiosemicarbazide <SEP> | <SEP> HH <SEP><SEP> - <SEP> Cl <SEP> - <SEP > NH <SEP> l
<tb> I <SEP> I <SEP> I <SEP> I <SEP> s
<tb> I <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb> 1 <SEP> 6 <SEP> 1 <SEP>"<SEP> I <SEP> 4-methyl-3-thiose- <SEP> | <SEP> HH <SEP> j <SEP> - <SEP> C <SEP> - <SEP> NH <SEP> - <SEP> CH <SEP> j
<tb><SEP> ti <SEP> \ 1 <SEP> 3
<tb> I <SEP> I <SEP> j <SEP> micarbazide <SEP> | <SEP> | <SEP> I <SEP> S <SEP> l
<Tb>
TABLE 1 (continued)

<tb> I <SEP> - <SEP> I <SEP> 4 <SEP> I
<tb> l <SEP> l <SEP>&verbar;<SEP> 4 <SEP> l
<tb> It <SEP> R <SEP> I
<tb> J <SEP> I <SEP> I <SEP> Zemeligand <SEP> of <SEP> formula <SEP> H <SEP> NN
<tb><SEP> Z <SEP> \ 5
<tb> j <SEP> EX <SEP> j <SEP> 1st <SEP> ligand <SEP> I <SEP> j <SEP> -2 <SEP> R <SEP> j
<tb> l <SEP> l <SEP> | <SEP> (5.10 <SEP> å <SEP> 1.10 <SEP> mmol / l)
<tb> l ~~~~~~~~~~~~~~~~~ l ~~~~~~~~~~~~~~~~~~~~~~~~~~ ~~~~~~~~~~~~~~~~~ the
<tb> It <SEP> I <SEP> 141 <SEP> 5 <SEP> I
<tb> I <SEP> I <SEP> j <SEP> NAME <SEP> j <SEP> R <SEP> NAME <SEP> | <SEP> R <SEP> | <SEP> R
<tb> I <SEP> l <SEP> l ~~~~~~~~~~~~~~~~~~~ l ~~~~~ l ~~~~~~~~~~~ ~~~~~ the
<tb> It <SEP> I <SEP> I <SEP> I
<tb> 7 <SEP> 1 <SEP> 7 <SEP> | <SEP> triphenyl <SEP> 1 <SEP> carbohydrazide <SEP> | <SEP> H <SEP> | <SEP> H <SEP> j <SEP> - <SEP> C <SEP> - <SEP> NH <SEP> -.NH <SEP> j
<tb><SEP> It <SEP> Z
<tb> I <SEP> I <SEP> phosphine <SEP> I <SEP> l <SEP> I <SEP> o <SEP> j
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I
<tb> 1 <SEP> 8 <SEP> 1 <SEP>"<SEP> | <SEP> I <SEP> | <SEP> thiocarbohydrazide <SEP> | <SEP> HH <SEP> j <SEP> - <SEP > C <SEP> - <SEP> NH <SEP> - <SEP> NH2 <SEP> j
<tb> I <SEP> I <SEP> I <SEP> I
<tb> It <SEP> I <SEP> I <SEP> 1 <SEP> I
<tb> 1 <SEP> 9 <SEP> 1 <SEP> | <SEP> acethydrazide <SEP> | <SEP> H <SEP> H <SEP> d <SEP> - <SEP> C <SEP> - <SEP> CH3 <SEP>
<tb> It <SEP> I <SEP> j <SEP> j0u <SEP> 3
<tb> It <SEP> j <SEP> I <SEP> 1 <SEP> I
<tb> j <SEP> 10 <SEP> j <SEP>"<SEP> | <SEP>"<SEP> | <SEP> methyl <SEP> hydrazine <SEP> | <SEP> H <SEP> N <SEP> j <SEP> - <SEP> C <SEP> - <SEP> OCH <SEP> j
<tb><SEP> n
<tb><SEP> I <SEP><SEP> carboxylate <SEP> I <SEP> | <SEP> o <SEP> I <SEP> 0
<tb> I <SEP> j <SEP> I <SEP> I
<tb> I <SEP> 11 <SEP> I <SEP> I <SEP> 11 <SEP> | <SEP>&commat;<SEP> | <SEP> furoyl-2-hydrazide <SEP> | <SEP> H <SEP> H <SEP> j <SEP> - <SEP> - <SEP> IÇ) iJ <SEP> I
<tb> I <SEP> I <SEP> o <SEP> ilool
<tb> It <SEP> I <SEP> I <SEP> l <SEP> l
<tb> 1 <SEP> 12 <SEP> 1 <SEP> 12 <SEP> | <SEP>"<SEP> | <SEP> Saiicyloyl <SEP> Hydra- <SEP> I <SEP> H <SEP> I <SEP> I <SEP> C <SEP> - <SEP> j
<tb> I <SEP> I <SEP> j <SEP> zide <SEP> j <SEP> J <SEP>z;; from <SEP> | <SEP> | <SEP> O <SEP> OH <SEP> j
<tb> It <SEP> j <SEP> j <SEP> I <SEP> I
<tb> 1 <SEP> 13 <SEP> 1 <SEP> 13 <SEP> | <SEP>"<SEP> | <SEP> aminoguanidine <SEP> | <SEP> H <SEP> H <SEP><SEP> - <SEP> C <SEP> - <SEP> NHZ <SEP>
<tb><SEP> n
<tb> I <SEP> I <SEP> I <SEP> j <SEP> j <SEP> NH
<tb> 1 ~~~~ 1 ~~~~~~~ ,,,, <SEP> I <SEP> j <SEP> I <SEP> I
<Tb>
TABLE 2

<tb> He <SEP>
<tb> 4 <SEP> I <SEP> I <SEP> liR <SEP> I
<tb> I <SEP> I <SEP> j <SEP> Z <SEP> ligand <SEP> R <SEP> - <SEP> CH <SEP> = <SEP> N <SEP> 5
<tb> I <SEP> R <SEP> I <SEP> R
<tb> I <SEP> EX <SEP> EX <SEP> | <SEP> I
<tb> It <SEP> 141 <SEP> 5 <SEP> j <SEP> 5 <SEP> I
<tb> I <SEP> I <SEP> j <SEP> | <SEP> | <SEP> NAME <SEP> | <SEP> R <SEP> | <SEP> R <SEP> | <SEP> R <SEP> j <SEP> R
<tb> 1 ,,,, 1 ,,, ~~~~~~~ -1 <SEP> I <SEP> j <SEP> I <SEP> I <SEP> I
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb> I <SEP> Itriphenyl <SEP> I <SEP> S-methylt-N (2-hy- <SEP> I <SEP> | - <SEP> C <SEP> I- <SEP> C <SEP> - <SEP> SCH <SEP> j
<tb> I <SEP> 14 <SEP> | phosphine <SEP> j <SEP> droxyphenyl) methyl-I <SEP> H <SEP> | <SEP> S <SEP> l <SEP> It
<tb> S
<tb> I <SEP>(<SEP> I <SEP> ne <SEP> dithiocarbazate <SEP> | <SEP> I
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I
<tb><SEP> I <SEP> I <SEP>"<SEP> n-methyl <SEP> S-methyl <SEP> j <SEP> j <SEP> I <SEP> I
<tb> I <SEP> 15 <SEP> j <SEP> I <SEP> | <SEP> | &Quot; SEP &quot;
<tb><SEP> 3
<tb><SEP> I <SEP> Imethylene <SEP> dithiocar- <SEP><SEP> I <SEP> I <SEP> I
<tb> I <SEP> I <SEP> bazate <SEP> j <SEP> j <SEP> I <SEP> I
<tb> I <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb> I <SEP> I <SEP>"<SEP> I <SEP>, N-methyl-S-methyl <SEP> I <SEP> I <SEP> I <SEP> I
<tb> 1 <SEP> 16 <SEP> 1 <SEP> I <SEP> | <SEP> | <SEP> -N <SEP> pyridylmethylene <SEP> e <SEP>"<SEP>"<SEP><SEP> I <SEP> IQ
<tb> I <SEP> I <SEP> Idithiocarbazate <SEP> I <SEP> I <SEP> IINI
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I
<tb><SEP> Idiethyl <SEP> 18-methyl <SEP> | S-methyl <SEP>, N (2-hy- <SEP> | <SEP> | <SEP> 1 <SEP> n
<tb> 1 <SEP> 17 <SEP> Iphenyl <SEP> Idrophenyl) <SEP> methylene <SEP> I <SEP> H <SEP> 1I <SEP> H <SEP> | <SEP> 1XI
<tb> I <SEP> Iphosphine <SEP> Idithiocarbazate <SEP> I <SEP> I <SEP> jHj
<tb> l <SEP> l <SEP> l <SEP> l <SEP> l <SEP> l
<Tb>
TABLE 2 (Continued)

<tb> ------------- """'""""""""""
<tb> I <SEP> I <SEP> I
<tb> II <SEP> I <SEP> | <SEP> 11 <SEP> R <SEP> R
<tb> I <SEP> I <SEP> 2nd <SEP> ligand <SEP> R <SEP> - <SEP> CH <SEP> = <SEP> N
<tb> I <SEP> I <SEP> | <SEP> R <SEP> 5
<tb> J <SEP> EX <SEP> I <SEP> 1st <SEP> ligand | ~~~~~~~~~~~~ <SEP> Ligandj <SEP> I
<tb> He <SEP> 141 <SEP> 5 <SEP> He
<tb> I <SEP> | <SEP> | <SEP> NAME <SEP> NAME <SEP> 4 <SEP> 1 <SEP> 5 <SEP> R <SEP> 11
<tb> I <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I
<tb> I <SEP> Riphenyl <SEP> Is-methyl- <SEP> J3, N (2,5- <SEP> 1 <SEP> I <SEP> i <SEP> t
Phosphine (SEP) (dihydroxyphenyl) (SEP)>SEP> H <SEP><SEP> C <SEP> - <SEP> SCH <SEP> ol <SEP> 18 <SEP> Phosphine
<tb> I <SEP> 18 <SEP> | phosphine <SEP> | dShydroxy-phenyl) <SEP> | <SEP> H <SEP> | - <SEP> It <SEP> 3 <SEP> It
<tb><SEP> | methylene <SEP> dithiocar- <SEP> | <SEP> t <SEP> s <SEP> I <SEP> r
<tb> I <SEP> I <SEP> Ibazate <SEP> I <SEP> I <SEP> IHO <SEP> I
<tb> It <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb> j <SEP> Idiytyt <SEP> j <SEP> I <SEP> I <SEP> I <SEP> I
<tb> i <SEP> 19 <SEP> Iphenyl <SEP> I <SEP><SEP> I <SEP>"<SEP> I <SEP>"<SEP> I <SEP>'I<SEP> I
<tb> I <SEP> Iphosphine <SEP><SEP> I <SEP> I <SEP> I <SEP> I
<tb> I <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb><SEP> 20 <SEP> Itriethyl <SEP> I <SEP>, <SEP> I <SEP>"<SEP> I <SEP>"<SEP> It <SEP> j
<tb> I <SEP> Iphosphine <SEP> I <SEP> I <SEP> I <SEP> j <SEP> I
<tb> II <SEP> I <SEP> I <SEP> I <SEP> I <SEP> I
<tb>(<SEP> 21 <SEP> Itrimethyl <SEP> I <SEP> I <SEP> I <SEP> I <SEP>"<SEP>"<SEP> CI <SEP> j
<tb> I <SEP> Iphosphine <SEP> j <SEP> I <SEP> I <SEP> J <SEP> I
<tb> 1 ,,,, 1 <SEP> j <SEP> I <SEP> I <SEP> I <SEP> I
<Tb>

Claims (22)

 A process for preparing a product comprising a nitrido complex of a transition metal having a portion MEN with M representing the transition metal, characterized in that an oxygenated compound of the transition metal M is reacted with a first ligand selected from the group of aliphatic and aromatic phosphines and polyphosphines, and a second nitrogen ligand comprising a motif in which the Ns are connected to hydrogen atoms and / or monovalent organic groups via a carbon atom or in which one of the N is linked to the carbon atom d a divalent organic group via a double bond and the other N is connected to hydrogen atoms and / or monovalent organic groups via a carbon atom.  2. A process for the preparation of a product comprising a nitrido complex of a transition metal comprising a part M = N in which M represents the transition metal, characterized in that an oxygen compound is reacted with the transition metal. M with: 1) - a first ligand selected from the group of phosphines and  aliphatic and aromatic polyphosphines, 2) - a second nitrogen ligand having a vN-Ns motif in  which the N's are connected to hydrogen atoms and / or  monovalent organic groups via  of a carbon atom, or in which one of the N is connected to  the carbon atom of a divalent organic group by  via one double link and the other N is connected  to hydrogel atoms and / or organic groups  monovalents via a carbon atom, and 3) - a third organic ligand with a nucleophilic group,  a monoclonal antibody or an antibody fragment.  3. Process according to claim 1, characterized in that, in a first stage, the oxygenated compound of the transition metal is reacted with the first and second ligands, and, in a second step, the product obtained is reacted with following the first step with the third ligand, the monoclonal antibody or the antibody fragment.  4. Method according to any one of claims 2 and 3, characterized in that the third ligand is selected from amines, thiols, thioethers, oximes, phosphines and polyfunctional ligands of the polyaminopolythiol type.  5. Method according to any one of claims 2 and 3, characterized in that the third ligand is selected from N, N'-bis (2-methylpropane-2-thiol) ethane, tetraazaundecane and 1,2, bis (dimethylphosphine) ethane hydrochloride.  6. Process according to any one of claims 1 to 5, characterized in that the transition metal is technetium.  7. Process according to claim 6, characterized in that the oxygenated compound of the transition metal is an alkali metal or ammonium pertechnetate.  8. Process according to any one of claims 1 to 5, characterized in that the transition metal is rhenium.  9. Process according to claim 8, characterized in that the oxygenated compound of the transition metal is alkali metal or ammonium perrhenate.  in which R, R and R, which may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical or an alkyl or aryl radical substituted by a group chosen from amino radicals. or amido.

 10. Process according to any one of claims 1 to 9, characterized in that the first ligand is a phosphine corresponding to the formula  11. Method according to any one of claims 1 to 9, characterized in that the first ligand is a nolvohosohine corresponding to the formulas:

 In which R and R, which may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical or an alkyl or aryl radical substituted with a group chosen from amino and amido radicals. , and m is an integer from 1 to 4.  12. The method of claim 10, characterized in that the first ligand is a phosphine selected from triphenylphosphine, diethylphenylphosphine, triethylphosphine and trimethylphosphine.  13. Process according to any one of Claims 1 to 12, characterized in that the second ligand corresponds to the formula:

 Wherein R, R, R and R, which may be the same or different, represent a hydrogen atom; an alkyl radical; an aryl radical; an alkoxy radical; an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals; an aryl radical substituted with at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical; a radical corresponding to the formulas:

 ZZ substituted or substituted by at least one group selected from halogen atoms and hydroxyl, alkoxy, amino, mercapto and amino radicals substituted by at least one alkyl radical, or a radical derived from an unsubstituted heterocycle or substituted by a or more groups selected from halogen atoms and hydroxy, alkoxy, amino, mercavo and amino radicals substituted by at least one alkyl radical and, R represents an hydrogen atom, an alkyl radical or an alkyl radical substituted by at least one group selected from hydroxy, carboxy, amino, amido and mercapto; and R and R have the meaning given above.  Wherein R represents -CH-NH, an aryl radical not

 Hydroxy groups; or wherein R and R may together form a divalent radical of formula R representing an alkyl radical, an alkoxy radical, an aryl radical which is unsubstituted or substituted by at least one group chosen from halogen atoms and hydroxyl radicals, or a radical derived from an unsubstituted heterocycle or substituted by at least one group selected from halogen atoms and  wherein R10 represents a hydrogen atom, an alkyl radical or an aryl radical; a radical of formula R -CO- with it

 Wherein R and R, which may be the same or different, represent a hydrogen atom, an alkyl radical, or an amino radical; a radical of formula  14. Process according to any one of Claims 1 to 12, characterized in that the second ligand is dithiocarbazic acid or a derivative thereof having the formula

 in which R10 represents a hydrogen atom, a radical  Alkyl or an aryl radical, and R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals; or an aryl radical substituted with at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical.  15. Process according to any one of claims 1 to 12, characterized in that the second ligand is a condensation product of dithiocarbazic acid corresponding to the formula

R and R, which may be identical or different, represent a hydrogen atom, an alkyl radical or an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals.  In which R represents a hydrogen atom, an alkyl radical or an aryl radical, R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical or an alkyl radical substituted by at least one chosen group. among the hydroxyl, caboxy, amino, amido and mercapto radicals, or an aryl radical substituted by at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, Rercapto and amino radicals substituted by at least one alkyl radical; and  16. Process according to any one of Claims 1 to 12, characterized in that the second ligand is a condensation product of dithiocarbazic acid corresponding to the formula: in which

 an alkyl radical or an aryl radical; R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals, or an aryl radical substituted by at least one a group chosen from halogen atoms and alkoxy, hydroxy, amino mercapto and amino radicals substituted by at least one alkyl radical; R represents a hydrogen atom, an alkyl radical, an alkyl radical substituted by at least one chosen group; from 1g hydroxy, carboxy, amino, amido and mercapto radicals, R represents a hydrogen atom, a halogen atom, an alkoxy radical, an amino radical, or an amino radical substituted by at least one alkyl group, R represents an atom of hydrogen, a hydroxy radical or a mercapto radical, E represents a carbon atom or a nitrogen atom, and n is an integer ranging from  18 of 1 to 4, or wherein n is 2 and the two R's are adjacent and together form an aromatic ring.  17. Process according to any one of Claims 1 to 12, characterized in that the second ligand is a condensation product of dithiocarbazic acid corresponding to the formula

 18 hydroxy, carboxy, amino, amido and mercapto radicals, R represents a hydrogen atom, a halogen atom, an alkoxy radical, an amino radical, or an amino radical substituted by at least one alkyl group, G is S or 0, and p is 1, 2 or 3.  Wherein R represents a hydrogen atom, an alkyl radical or an aryl radical; R represents a hydrogen atom, an alkyl radical, an aryl radical, an alkoxy radical, an alkyl radical substituted with at least one group chosen from hydroxyl, carboxy, amino, amido and mercapto radicals, or an aryl radical substituted with at least one group chosen from halogen atoms and alkoxy, hydroxy, amino, mercapto and amino radicals substituted by at least one alkyl radical; R represents a hydrogen atom, an alkyl radical or an alkyl radical substituted by at least one group; chosen from  18. Process according to any one of claims 1 to 12, characterized in that the second ligand is hydrazine or a hydrazine derivative corresponding to the formula:  20 21  R -NH-NH-R  Wherein R is a hydrogen atom or an alkyl radical  And R is a hydrogen atom or a radical selected from the radicals of formula:

 In which R and R, which may be the same or different, represent a hydrogen atom, an alkyl radical or an amino radical, R represents an alkyl radical and R represents an aryl radical which is unsubstituted or substituted by at least one group chosen from halogen atoms and hydroxyl radicals or a radical derived from a heterocycle which is unsubstituted or substituted by at least one group chosen from halogen atoms and hydroxyl radicals.  19. Method according to any one of claims 1 to 12, characterized in that the second ligand is chosen from S-methyl-beta-N (2-hydroxyphenyl) methylene dithiocarbazate, S-methyldithiocarbazate, 5-methyl N methyldithiocarbazate, alpha-N-methyl-S-methyl beta-N-pyridylmethylene dithiocarbazate, S-methyl-beta-N- (Zh-hydroxyphenyl) methylene dithiocarbazate and alpha-N-methyl-S-methyl-beta -N (2-hydroxyphenyl) methylene dithiocarbazate.  20. Process according to any one of claims 1 to 12, characterized in that the second ligand is chosen from hydrazine, semicarbazide, thiosemicarbazide, 1-methyl-3-thiosemicarbazide, 4-methyl-3- thiosemicarbazide, aminoacetonesemicarbazone, carbohydrazide, thiocarbohydrazide, acethydrazide, methylhydrazinecarboxylate, furoyl-2 hydrazide, salicyloyl hydrazide and aminoguanidine.  21. A kit for the preparation of a nitrido complex of technetium by carrying out the process according to any one of claims 1 to 20, characterized in that it comprises: a first flask containing the first organic ligand; and a second vial containing the second organic ligand.  22. Kit according to claim 21, characterized in that it comprises a third flask containing a third organic ligand nucleophilic group.