Radiolabeled glucans covalently linked to a radiolabel binding moiety
AssigneeDiatide, Inc.
InventorRichard T. Dean
Life of this patent
Estimating the term…
Abstract
This invention relates to radiodiagnostic agents and reagents for preparing such agents, and also methods for producing radiolabeled radiodiagnostic agents. Specifically, the invention relates to technetium-99m (.sup.99m Tc) labeled agents, methods and kits for making the agents, and methods for using the agents to image pathological sites, including sites of infection, inflammation, cancer and atherosclerosis in a mammalian body. Specifically the agents and reagents are derivatives of oligosaccharides, more specifically .beta.-glucans.
Claims17
A scintigraphic imaging agent comprising a reagent comprising a specific-binding .beta.-glucan covalently linked to a radiometal-binding moiety, wherein the .beta.-glucan is linked to the moiety by a linkage selected from the group consisting of a direct covalent linkage and a linker having a molecular weight less than about 500 Da, and wherein the radiometal-binding moiety is attached to a radioisotope.
A scintigraphic imaging agent comprising a poly-.beta.1-6-glucotriosyl-.beta.1-3-glucopyranose covalently linked to a radiometal-binding moiety.
A complex formed by reacting a reagent comprising a .beta.-glucan covalently linked to a radiometal binding moiety, wherein the .beta.-glucan is linked to the moiety by a linkage selected from the group consisting of a direct covalent linkage and a linker having a molecular weight less than about 500 Da, with .sup.99m Tc in the presence of a reducing agent.
A complex formed by labeling a reagent comprising a .beta.-glucan covalently linked to a radiometal binding moiety, wherein the .beta.-glucan is linked to the moiety by a linkage selected from the croup consisting of a direct covalent linkage and a linker having a molecular weight less than about 500 Da, with .sup.99m .sup.99m Tc by ligand exchange of a prereduced .sup.99m Tc complex.
A method for labeling a reagent comprising a .beta.-glucan covalently linked to a radiometal binding moiety, wherein the .beta.-glucan is linked to the moiety by a linkage selected from the group consisting of a direct covalent linkage and a linker having a molecular weight less than about 500 Da, comprising the step of reacting the reagent with .sup.99m Tc in the presence of a reducing agent.
A complex formed by labeling a reagent comprising a poly-.beta.1-6-glucotriosyl-.beta.1-3-glucopyranose covalently linked to a radiometal-binding moiety with .sup.99m Tc by ligand exchange of a prereduced .sup.99m Tc complex.
A complex formed by labeling a reagent comprising a .beta.-glucan covalently linked to a radiometal-binding moiety having a formula selected from the group consisting of:
- (a) C(pgp).sup.S -(aa)-C(pgp).sup.S
- wherein (pgp).sup.S is H or a thiol protecting group and (aa) is any primary .alpha.- or .beta.-amino acid;
- (b) a radiometal complexing group comprising a single thiol moiety having a formula:
- A--CZ(B)--C(R'R")!.sub.n --X
- wherein
- A is H, HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC or R"";
- B is H, SH, --NHR'", --N(R'")-(linker)-(.beta.-glucan), or R"";
- X is H, SH, --NHR'", --N(R'")-(linker)-(.beta.-glucan) or R"";
- Z is H or R"";
- R', R", R'" and R"" are independently H or lower straight or branched chain or cyclic alkyl;
- n is 0, 1 or 2;
- and
- where B is --NHR'" or --N(R'")-(linker)-(.beta.-glucan), X is SH, and n is 1 or 2;
- where X is --NHR'" or --N(R'")-(linker)-(.beta.-glucan), B is SH, and n is 1 or 2;
- where B is H or R"", A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC, X is SH, and n is 0 or 1;
- where A is H or R"", then where B is SH, X is --NHR'" or --N(R'")-(linker)-(.beta.-glucan) and where X is SH, B is --NHR'" or --N(R'")-(linker)-(.beta.-glucan);
- where X is H or R"", A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC and B is SH;
- where Z is methyl, X is methyl, A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC, B is SH and n is 0;
- and wherein (.beta.-glucan) represents the covalent attachment of the
- radiometal binding moiety to the .beta.-glucan;
- (c) ##STR5## wherein X=H or a protecting group;
- (amino acid)=any amino acid;
- (d) ##STR6## wherein X=H or a protecting group;
- (amino acid)=any amino acid;
- (e) ##STR7## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- and
- (f) ##STR8## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- m, n and p are independently 2 or 3;
- A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or --CO--(linker)-(.beta.-glucan);
- R'=H or (linker)-(.beta.-glucan);
- and wherein when V=H, R'=-(linker)-(.beta.-glucan) and when R'=H, V=--CO--(linker)-(.beta.-glucan);
- wherein (linker) is a bond or a divalent radical covalently attached to the .beta.-glucan and to the radiolabel-binding moiety and wherein (.beta.-glucan) represents the covalent attachment of the radiometal binding moiety to the .beta.-glucan
- with .sup.99m Tc by ligand exchange of a prereduced .sup.99m Tc complex.
A complex formed by labeling a reagent comprising a poly-.beta.1-6-glucotriosyl-.beta.1-3-glucopyranose covalently linked to a radiometal-binding moiety with .sup.99m Tc in the presence of a reducing agent.
A complex formed by labeling a reagent comprising a .beta.-glucan covalently linked to a radiometal-binding moiety having a formula selected from the group consisting of:
- (a) C(pgp).sup.S -(aa)-C(pgp).sup.S wherein (pgp).sup.S is H or a thiol protecting group and (aa) is any primary .alpha.- or .beta.-amino acid;
- (b) a radiometal complexing group comprising a single thiol moiety having a formula:
- A--CZ(B)-C(R'R")!.sub.n -X
- wherein
- A is H, HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC or R"";
- B is H, SH, --NHR'", --N(R'")-(linker)-(.beta.-glucan), or R"";
- X is H, SH, --NHR'", --N(R'")-(linker)-(.beta.-glucan) or R"";
- Z is H or R"";
- R', R", R'" and R"" are independently H or lower straight or branched chain or cyclic alkyl;
- n is 0, 1 or 2;
- and
- where B is --NHR'" or --N(R'")-(linker)-(.beta.-glucan), X is SH, and n is 1 or 2;
- where X is --NHR'" or --N(R'")-(linker)-(.beta.-glucan), B is SH, and n is 1 or 2;
- where B is H or R"", A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC, X is SH, and n is 0 or 1;
- where A is H or R"", then where B is SH, X is --NHR'" or --N(R'")-(linker)-(.beta.-glucan) and where X is SH, B is --NHR'" or --N(R'")-(linker)-(.beta.-glucan);
- where X is H or R"", A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC and B is SH;
- where Z is methyl, X is methyl, A is HOOC, H.sub.2 NOC, (.beta.-glucan)-(linker)-NHOC, (.beta.-glucan)-(linker)--OOC, B is SH and n is 0;
- and wherein (.beta.-glucan) represents the covalent attachment of the radiometal binding moiety to the .beta.-glucan;
- (c) ##STR9## wherein X=H or a protecting group;
- (amino acid)=any amino acid;
- (d) ##STR10## wherein X=H or a protecting group;
- (amino acid)=any amino acid;
- (e) ##STR11## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- and
- (f) ##STR12## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- m, n and p are independently 2 or 3;
- A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or --CO--(linker)-(.beta.-glucan);
- R'=H or (linker)-(.beta.-glucan);
- and wherein when V=H, R'=-(linker)-(.beta.-glucan) and when R'=H, V=--CO--(linker)-(.beta.-glucan);
- wherein (linker) is a bond or a divalent radical covalently attached to the .beta.-glucan and to the radiolabel-binding moiety and wherein (.beta.-glucan) represents the covalent attachment of the radiometal binding moiety to the .beta.-glucan;
- with .sup.99m Tc in the presence of a reducing agent.
Dependencies are inferred from the claim text.