Claims
- 1. Method of preparing a compound of the general formulafac-[M(CO)3(OH2)3]+ (I) wherein M is Mn, 99mTc, 186Re or 188Re,by reacting a metal in the permetallate form with carbon monoxide and a reducing agent, characterized in that a mixture of a base, a reducing agent soluble in water but not substantially decomposed by water, and optionally a stabilizing agent is solved in a water containing solvent system containing a solution of the metal in the permanganate, pertechnetate or perrhenate form in the presence of carbon monoxide.
- 2. Method of preparing a compound of the general formulafac-[M(CO)3(X)2L1]n (II), fac-[M(CO)3(X)L1]n (III) orfac-[M(CO)3L3]n (IV), wherein:M is Mn, 99mTc, 186Re or 188Re; L1 is a monodentate ligand, L2 is selected from the group consisting of a bidentate ligand and two monodentate ligands, and L3 is selected from the group consisting of a tridentate ligand, a monodentate ligand and a bidentate ligand, and three monodentate ligands; X is H2O or a halide ion; n is the sum of the charge of the ligands L1 or L2 or L3 and X increased with one + charge; characterized in that a compound of the general formulafac-[M(CO)3(OH2)3]+ (I) prepared by reacting a metal in the permetallate form with carbon monoxide and a reducing agent, wherein a mixture of a base, a reducing agent soluble in water but not substantially decomposed by water, and optionally a stabilizing agent is solved in a water containing solvent system containing a solution of the metal in the permanganate, pertechnetate or perrhenate form in the presence of carbon monoxide, is reacted with ligands L1, L2 or L3, optionally in the presence of a halide.
- 3. Method of preparing a compound of the general formulafac-[M(CO)3(X)2L1]n (II), fac-[M(CO)3(X)L2]n (III) orfac-[M(CO)3L3]n (IV), wherein:M is Mn, 99mTc, 186Re or 188Re; L1 is a monodentate ligand, L2 is selected from the group consisting of a bidentate ligand and two monodentate ligands, and L3 is selected from the group consisting of a tridentate ligand, a monodentate ligand and a bidentate ligand, and three monodentate ligands; X is H2O or a halide ion; n is the sum of the charge of the ligands L1 or L2 or L3 and X increased with one + charge; characterized in that a mixture of a base, ligands L1 or L2 or L3, a reducing agent soluble in water but not substantially decomposed by water, and optionally a stabilizing agent is dissolved in a water containing solvent system containing a solution of the metal in the permanganate, pertechnetate or perrhenate form in the presence of carbon monoxide and optionally in the presence of a halide.
- 4. Method according to claim 2 or 3, characterized in that the ligands L1-L3 are derived from biologically active substrates selected from the group consisting of amino acids, peptides, proteins, sugars, small receptor binding molecules and body cells.
- 5. Method according to claim 4, characterized in that the substrate is an amino acid, a peptide or a protein.
- 6. Method according to claim 1 or 3, characterized in that the base is an inorganic base.
- 7. Method according to claim 1 or 3, characterized in that the molar ratio between the base and the reducing agent is between 0.1 and 2.
- 8. Method according to claim 1 or 3, characterized in that the reducing agent is selected from the group consisting of borohydride anion and substituted borohydride anion wherein up to three of the hydrogen atoms which comprise the borohydride anion have been replaced by inert substituents.
- 9. Method according to claim 8, characterized in that the reducing agent is a borohydride anion derived from of a salt selected from the group consisting of sodium borohydride, potassium borohydride, lithium borohydride and zinc borohydride.
- 10. Method according to claim 9, characterized in that the reducing agent is sodium borohydride.
- 11. Method according to claim 10, characterized in that the molar ratio of the reducing agent to the permetallate is at least 3.
- 12. Method according to claim 1 or 3, characterized in that the reaction temperature is between 20° C. and 100° C.
- 13. A kit for the preparation of labelling composition, comprising (i) a reducing agent soluble in water but not substantially decomposed by water, (ii) a base, (iii) if desired, a stabilizing agent and/or chelator and (iv) if desired one or more inert pharmaceutically acceptable carriers and/or formulating agents and/or adjuvants, at least one of said ingredients (i) to (iv) being stored in a container having an atmosphere containing a sufficient amount of carbon monoxide to form a complex of a formula M(CO)3, said ingredients (i) to (iv) optionally independently being combined, and (v) instructions for use with a prescription for reacting the ingredients of the kit with a metal selected from the group consisting of Mn, 99mTc, 186Re or 188Re in the form of a permetallate solution.
- 14. A kit for the preparation of a diagnostic pharmaceutical composition, comprising (i) a substrate to be labelled with a metal selected from the group consisting of Mn, 99mTc, 186Re or 188Re, (ii) a reducing agent soluble in water but not substantially decomposed by water, (iii) a base, (iv) if desired, a stabilizing agent and/or chelator, (v) if desired one or more inert pharmaceutically acceptable carriers and/or formulating agents and/or adjuvants, at least one of said ingredients (i) to (v) being stored in a container having an atmosphere containing a sufficient amount of carbon monoxide to form a complex of a formula M(CO)3, said ingredients (i) to (v) optionally independently being combined, and (vi) instructions for use with a prescription for reacting the ingredients of the kit with a metal in the form of a permetallate solution.
- 15. Method according to claim 1 or 3, characterized in that the base is an inorganic base selected from the group consisting of NaOH, KOH, NaHCO3, Na2CO3, KHCO3, K2CO3, Ca(OH)2 and Mg(OH)2.
- 16. Method according to claim 7, characterized in that the molar ratio between the base and the reducing agent is approximately 0.35.
- 17. Method according to claim 12, characterized in that the reaction temperature is approximately 75° C.
Priority Claims (1)
Number |
Date |
Country |
Kind |
97201232 |
Apr 1997 |
EP |
|
Parent Case Info
This application is a 371 of PCT/US98/07979, filed Apr. 21, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US98/07979 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/48848 |
11/5/1998 |
WO |
A |
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4935222 |
Deutsch et al. |
Jun 1990 |
A |
Non-Patent Literature Citations (2)
Entry |
Beck, W. et al., Mitallkomplexe mit biologisch wichtigen liganded, Jour. of Organometallic Chemistry, 191, pp. 73-77, 1980.* |
Alberto, R. et al., Metal carbonyl synethesis XXII, Journal of Organometallic Chemistry, 493, pp. 119-127, 1995. |