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Isonitrile radionuclide complexes for labelling and imaging agents

Assignee: Janssen Pharmaceutica NV
•
Filing: 1982-04-30
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Granted: 1984-06-05
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Expires: 2002-04-30
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Abstract

Abstract A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.

Inventors

  • 👤 Alun G. Jones
  • 👤 Alan Davison
  • 👤 Michael J. Abrams

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-30 09:29
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/12; A61K51/1217; A61K51/1234; A61K51/02; A61K51/025; C; C07; C07C; C07C251/00; C07F; C07F13/00; C07F13/005; A61K2123/00

Claims Analysis

Total Claims: 43
Claim 1
Independent Claim 38 words
A coordination complex of an isonitrile ligand and a radioactive metal selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb, and Ta.
Claim 2
Dependent Claim 38 words
A coordination complex of an isonitrile ligand and a radioactive metal selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb, and Ta.
Claim 3
Dependent Claim 13 words
A complex as claimed in claim 1 in which said metal is Tc.
Claim 4
Dependent Claim 13 words
A complex as claimed in claim 1 in which said metal is Re.
Claim 5
Dependent Claim 17 words
A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is aliphatic.
Claim 6
Dependent Claim 19 words
A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is a hydrocarbon isonitrile.
Claim 7
Dependent Claim 20 words
A complex as claimed in claim 1, 2 or 3 in which said isonitrile ligand is a saturated hydrocarbon isonitrile.
Claim 8
Dependent Claim 21 words
A complex as claimed in claim 1 wherein each coordinate position of said radioactive metal is filled by an isonitrile ligand.
Claim 9
Dependent Claim 15 words
A complex as claimed in claim 1 wherein said isonitrile ligand is a monodentate ligand.
Claim 10
Dependent Claim 15 words
A complex as claimed in claim 1 wherein said isonitrile ligand is a bidentate ligand.
Claim 11
Dependent Claim 15 words
A complex as claimed in claim 1 wherein said isonitrile ligand is a tridentate ligand.
Claim 12
Dependent Claim 15 words
A complex as claimed in claim 1 wherein said complex is a cationic lipophilic complex.
Claim 13
Dependent Claim 24 words
A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of Tc, Ru, Co, Pt, Fe, Os or Ir.
Claim 14
Dependent Claim 21 words
A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of W, Re, Fe or Os.
Claim 15
Dependent Claim 31 words
A complex as claimed in claim 1 wherein said radioactive metal is a radioactive isotope of Cr, Mo, Co, Tc, Fe, Mn, W, Ru, Ni, Rh, Ir, Pd, Nb or Ta.
Claim 16
Dependent Claim 152 words
An isonitrile complex having the formula: [A((CN).sub.x R).sub.y B.sub.z B'.sub.z' ].sup.n wherein A is a radionuclide selected from radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Ta; (CN) x R is a monodentate or polydentate isonitrile ligand bonded to the radionuclide through the carbon atom of the CN group; R is an organic radical; B and B' are independently other ligands selected from the class of solvents, halogen groups, and ligands comprising one or more neutral donor atoms capable of forming coordinant bonds with said radionuclide; x and y are each independently, integers from 1 to 8; z and z' are each independently 0 or an integer from 1 to 7; with the proviso that (xy)+z+z' is less than or equal to 8; and n indicates the charge of the complex and can be 0 (neutral), or a positive or negative integer.
Claim 17
Dependent Claim 152 words
An isonitrile complex having the formula: [A((CN).sub.x R).sub.y B.sub.z B'.sub.z' ].sup.n wherein A is a radionuclide selected from radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Ta; (CN) x R is a monodentate or polydentate isonitrile ligand bonded to the radionuclide through the carbon atom of the CN group; R is an organic radical; B and B' are independently other ligands selected from the class of solvents, halogen groups, and ligands comprising one or more neutral donor atoms capable of forming coordinant bonds with said radionuclide; x and y are each independently, integers from 1 to 8; z and z' are each independently 0 or an integer from 1 to 7; with the proviso that (xy)+z+z' is less than or equal to 8; and n indicates the charge of the complex and can be 0 (neutral), or a positive or negative integer.
Claim 18
Dependent Claim 25 words
An isontrile complex having the formula; [A(CNR).sub.6 ].sup.+ wherein A is a radionuclide selected from technetium and 188 Re, and R is an organic radical.
Claim 19
Dependent Claim 25 words
An isontrile complex having the formula; [A(CNR).sub.6 ].sup.+ wherein A is a radionuclide selected from technetium and 188 Re, and R is an organic radical.
Claim 20
Dependent Claim 8 words
A cationic lipophilic hexakis t-butylisonitrile complex of technetium.
Claim 21
Dependent Claim 8 words
A cationic lipophilic hexakis t-butylisonitrile complex of technetium.
Claim 22
Dependent Claim 76 words
A kit for preparing a coordination complex of an isonitrile ligand and a radionuclide selected from the class consisting of radioactive isotope of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, said kit comprising a predetermined quantity of said isonitrile ligand and a predetermined quantity of a reducing agent capable of reducing a predetermined quantity of a preselected one of said radionuclides to form said complex.
Claim 23
Dependent Claim 76 words
A kit for preparing a coordination complex of an isonitrile ligand and a radionuclide selected from the class consisting of radioactive isotope of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, said kit comprising a predetermined quantity of said isonitrile ligand and a predetermined quantity of a reducing agent capable of reducing a predetermined quantity of a preselected one of said radionuclides to form said complex.
Claim 24
Dependent Claim 17 words
A kit as claimed in claim 18 wherein said isonitrile ligand and said reducing agent are lyophilized.
Claim 25
Dependent Claim 22 words
A kit as claimed in claim 18 wherein said lyophilized isonitrile ligand and reducing agent are contained in a sealed, sterilized container.
Claim 26
Dependent Claim 19 words
A kit as claimed in claim 18, 19 or 20 wherein said preselected radionuclide is an isotope of Tc.
Claim 27
Dependent Claim 19 words
A kit as claimed in claim 18, 19 or 20 wherein said preselected radionuclide is an isotope of Re.
Claim 28
Dependent Claim 36 words
A kit for converting a supply of 99m Tc-pertechnetate to a complex as claimed in claim 1, said kit comprising a supply of an isonitrile and a supply of a reducing agent capable of reducing technetium.
Claim 29
Dependent Claim 23 words
A kit as claimed in claim 23 in which said reducing agent is selected from the class consisting of dithionites and stannous salts.
Claim 30
Dependent Claim 17 words
A kit as claimed in claim 23 wherein said isonitrile ligand and said reducing agent are lyophilized.
Claim 31
Dependent Claim 22 words
A kit as claimed in claim 23 wherein said lyophilized isonitrile ligand and reducing agent are contained in a sealed, sterilized container.
Claim 32
Dependent Claim 23 words
A kit as claimed in claim 18 wherein said radioactive metal is radioactive isotope of Tc, Ru, Co, Pt, Fe, Os or Ir.
Claim 33
Dependent Claim 21 words
A kit as claimed in claim 18 wherein said radioactive metal is a radioactive isotope of W, Re, Fe, or Os.
Claim 34
Dependent Claim 26 words
A kit as claimed in claim 18 wherein said isotope of Cr, Mo, Co, Tc, Fe, Mn, W, Ru, Ni, Rh, Ir, Pd, Nb or Ta.
Claim 35
Independent Claim 40 words
A method for imaging body tissues comprising administering to an animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and 99m Tc, and detecting the localization of such complex in the body tissues by a gamma camera.
Claim 36
Independent Claim 40 words
A method for imaging body tissues comprising administering to an animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and 99m Tc, and detecting the localization of such complex in the body tissues by a gamma camera.
Claim 37
Dependent Claim 11 words
The method of claim 30 wherein said complex is 99m Tc-hexakis-t-butylisonitrile.
Claim 38
Dependent Claim 11 words
The method of claim 30 wherein said complex is 99m Tc-hexakis-iso-propylisonitrile.
Claim 39
Independent Claim 44 words
A method for detecting vascular emboli in an animal comprising administering to said animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and 99m Tc, and detecting the emboli by localization of said complex at said emboli with a gamma camera.
Claim 40
Independent Claim 44 words
A method for detecting vascular emboli in an animal comprising administering to said animal a radiopharmaceutical composition comprising a coordination complex of an isonitrile ligand and 99m Tc, and detecting the emboli by localization of said complex at said emboli with a gamma camera.
Claim 41
Dependent Claim 11 words
The method of claim 33 wherein said complex is 99m Tc-hexakis-t-butylisonitrile.
Claim 42
Dependent Claim 11 words
The method of claim 33 wherein said complex is 99m Tc-hexakis-iso-propylisonitrile.
Claim 43
Dependent Claim 27 words
A method for labeling a cell or liposome comprising incubating said cell or liposome with a coordination complex as claimed in claim 1 in a suitable medium.

References Cited (Backward Citations)

US4017596A Cited
US4197312A Cited
US4338248A Cited
US4363793A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1987-06-05 1987-12-05 1988-06-05 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1991-06-05 1991-12-05 1992-06-05 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1995-06-05 1995-12-05 1996-06-05 $7700.00 Window Closed / Lapsed

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