Labeled alginate conjugates for molecular imaging applications
View Patent ↗Described are bifunctional NOTA-based derivatives capable of conjugating with alginate and with metal ions, as well as NOTA-alginate conjugates which can be labeled with stable or radioactive metal ions. Also described are conjugation methods of the bifunctional NOTA-based linker with alginate, and methods of using radiometal-labeled NOTA-alginate conjugates or other radio-labeled alginate conjugates as imaging reagents.
1. An alginate conjugate having the formula:
wherein X is —(CH 2 ) m C(O)—, with m being 1, 2, or 3;
L is a linker selected from the group consisting of:
wherein n, n′ and n″ are each independently a number from 0 to 10;
Alg is alginic acid or an alginate salt; and
Y is a spacer directly attached to the reducing end unit of alginate or the carboxyl groups of the alginate polymer chain via the active nitrogen, and has the following structure:
wherein R is selected from the group consisting of hydrogen, alkyl, benzyl or an aromatic group;
or a pharmaceutically acceptable salt or solvate thereof.
2. The alginate conjugate of claim 1 , wherein the conjugate further comprises a stable or radioactive metal ion chelated by the 1,4,7-triazacyclononane-1,4,7-triacetic acid moiety of the conjugate.
3. The alginate conjugate of claim 2 , wherein the stable or radioactive metal ion comprises a gallium ion.
4. The alginate conjugate of claim 2 , wherein the radioactive metal ion comprises 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, or 111 In.
5. A method of imaging in a mammal comprising:
administering the alginate conjugate of claim 1 to a mammal; and
imaging the temporal and spatial distribution of the alginate conjugate.
6. The method of claim 5 , wherein the alginate conjugate further comprises a stable or radioactive metal ion chelated by the 1,4,7-triazacyclononane-1,4,7triacetic acid moiety of the conjugate.
7. The method of claim 6 , wherein the stable or radioactive metal ion comprises a gallium ion.
8. The method of claim 6 , wherein the radioactive metal ion comprises 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, or 111 In.
9. The method of claim 5 , wherein the alginate conjugated is partially cross-linked.
10. A method of imaging alginate deposition in a mammal comprising:
administering a mixture of and the alginate conjugate of claim 1 and partially calcium-cross-linked alginate to a mammal; and
imaging the temporal and spatial distribution of the alginate conjugate.
11. The method of claim 10 , wherein the alginate conjugate further comprises a stable or radioactive metal ion chelated by the 1,4,7-triazacyclononane-1,4,7-triacetic acid moiety.
12. The method of claim 11 , wherein the stable or radioactive metal ion comprises a gallium ion.
13. The method of claim 11 , wherein the radioactive metal ion comprises 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, or 111 In.
14. The method of claim 10 , wherein alginate conjugate is partially cross-linked.