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US 5,635,157 AGranted
Synthesis of 4-substituted-trans-1,2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and spect and pet imaging
OwnerRonnie C. Mease, Kathryn L. Kolsky +2inventors
InventorsRonnie C. Mease, Kathryn L. Kolsky, Leonard F. Mausner, Suresh C. Srivastava
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Abstract
Cyclohexyl chelating agents useful in forming antibody-metal conjugates useful for diagnostic and therapeutic purposes. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2-diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid.
Claims17
A diagnostic method comprising the steps of:
- conjugating a compound selected from the group consisting of 4-amino-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, 4-isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, and trans-1,2-di[bis(carboxymethyl)amino]-4-haloacetamido-cyclohexane with an antibody or a bioactive peptide and a radioactive metal to form a radioimmunoconjugate;
- administering an imaging effective amount of said radioimmunoconjugate to a mammal wherein said radioimmunoconjugate selectively localizes in a target region of said mammal;
- and
- detecting radiation emitted by said radioimmunoconjugate.
1 more element
A diagnostic method comprising the steps of:
- providing trans-1,2-di[bis(carboxymethyl)amino]-4-amino-cyclohexane hydrochloride;
- contacting said trans-1,2-di[bis(carboxymethyl)amino]-4-amino-cyclohexane hydrochloride with LiOH to form a first solution;
- concentrating said first solution to a salt and reconstituting said salt in methanol to form a reconstituted solution;
- contacting said reconstituted solution with thiophosgene in CH.sub.2 Cl.sub.2 to form 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid;
- conjugating said 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid with an antibody or bioactive peptide and a radioactive metal to form a radioimmunoconjugate;
- administering an imaging effective amount of said radioimmunoconjugate to a mammal wherein said conjugate selectively localizes in a target region of said mammal;
- and
- detecting radiation emitted by said radioimmunoconjugate.
5 more elements
A method for radioimmunotherapy of cancer cells comprising the steps of:
- providing trans-1,2-di[bis(carboxymethyl)amino]-4-amino-cyclohexane hydrochloride;
- contacting said trans-1,2-di[bis(carboxymethyl)amino]-4-amino-cyclohexane hydrochloride with LiOH to form a first solution;
- concentrating said first solution to a salt and reconstituting said salt in methanol to form a reconstituted solution;
- contacting said reconstituted solution with thiophosgene in CH.sub.2 Cl.sub.2 to form 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid;
- conjugating said 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid with an antibody or bioactive peptide and a beta emitting radioactive metal to form a radioimmunoconjugate;
- administering an imaging effective amount of said radioimmunoconjugate to a mammal wherein said radioimmunoconjugate selectively localizes in a target region containing said cancer cells of said mammal.
3 more elements
A diagnostic method comprising the steps of:
- conjugating trans-1,2-di[bis(carboxymethyl)amino]-4-haloacetamido-cyclohexane with an antibody or bioactive peptide and a radioactive metal to form a radioimmunoconjugate;
- administering an imaging effective amount of said radioimmunoconjugate to a mammal wherein said radioimmunoconjugate selectively localizes in a target region of said mammal;
- and
- detecting radiation emitted by said radioimmunoconjugate.
1 more element
A diagnostic method comprising the steps of:
- contacting a compound selected from the group consisting of 4-amino-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, 4-isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, and trans-1,2-di[bis(carboxymethyl)amino]-4-haloacetamido-cyclohexane with an antibody or bioactive peptide in dimethyl sulfoxide to form an immunoconjugate;
- labeling said immunoconjugate with a radioactive metal to form a radioimmunoconjugate;
- administering an imaging effective amount of said radioimmunoconjugate to a mammal wherein said radioimmunoconjugate selectively localizes in a target region on said mammal;
- and
- detecting radiation emitted by said radioimmunoconjugate.
2 more elements
A delivery system for radioimmunotherapy which comprises:
- a chelating compound selected from the group consisting of 4-amino-trans-1,2-diaminocyclohexane-N,N,N,N'-tetraacetic acid, 4-isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid, and trans-1,2-di[bis(carboxymethyl)amino]-4-haloacetamido-cyclohexane;
- an antibody or bioactive peptide and a beta emitting radioactive metal conjugated to said chelating compound, wherein said chelating compound conjugates with said antibody or said bioactive peptide at the 4-substituted position.
Dependencies are inferred from the claim text.