Compositions useful for reducing toxicity associated with gadolinium-based contrast agents

1. A composition comprising a gadolinium-based contrast agent and a derivatized cyclodextrin wherein

the molar ratio of said agent to said cyclodextrin is from about 2:1 to 50:1;

wherein the gadolinium-based contrast agent is selected from the group consisting of gadodiamide, gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol, gadoxetic acid disodium salt, gadofosveset trisodium, gadobutrol, and gadoterate meglumine; and

wherein

said derivatized cyclodextrin is of the formula:

cyclodextrin-[(O—R—Y) − (Me) + ] n

where R is selected from the group consisting of straight-chained or branched C 1-10 alkyl, alkenyl or alkynyl; C 3-8 cycloalkyl and C 3-8 aryl, each ring optionally containing a heteroatom selected from S, N and O; and optionally substituted with halo or hydroxyl;

Y is an anionic group selected from the group consisting of COO, SO 4 , SO 3 , PO 3 H and PO 4 ;

Me is a pharmaceutically acceptable cation; and

n is a number greater than or equal to 1; and

wherein said derivatized cyclodextrin is present in an amount effective for inhibiting the toxic effect of said agent.

2. The composition of claim 1 , wherein the composition consists essentially of the gadolinium-based contrast agent and the derivatized cyclodextrin.

3. The composition of claim 1 further comprising a pharmaceutically acceptable carrier or diluent.

4. The composition of claim 1 wherein said cyclodextrin of the formula cyclodextrin-[(O—R—Y) − (Me) + ] n is an alpha-, beta-, or gamma-cyclodextrin.

5. The composition of claim 4 wherein R is C 1-10 alkyl and Y is SO 3 , such that the derivatized cyclodextrin is a sulfoalkyl ether cyclodextrin.

6. The composition of claim 1 wherein the molar ratio of the gadolinium-based contrast agent to the sulfoalkyl ether cyclodextrin is from 2:1 to about 10:1.

7. The composition of claim 1 wherein the derivatized cyclodextrin is sulfobutyl ether beta-cyclodextrin and the cyclodextrin of the formula cyclodextrin-[(O—R—Y) − (Me) + ] n is beta-cyclodextrin, O—R—Y) − is O—(CH 2 ) 4 —SO 3 , Me is sodium, and n is about 7.

8. A composition comprising a gadolinium-based contrast agent and a derivatized cyclodextrin wherein,

the gadolinium-based contrast agent is selected from the group consisting of gadodiamide, gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol, gadoxetic acid disodium salt, gadofosveset trisodium gadobutrol, and gadoterate meglumine;

the molar ratio of said agent to said cyclodextrin is from about 2:1 to 50:1; and wherein

said derivatized cyclodextrin is of the formula:

cyclodextrin-[O—R] n

where R is selected from the group consisting of straight-chained or branched C 1-10 alkyl, alkenyl or alkynyl; C 3-8 cycloalkyl and C 3-8 aryl, each ring optionally containing a heteroatom selected from S, N and O; and R is substituted with one or more hydroxyl groups; and

n is a number greater than or equal to 1; and

wherein said derivatized cyclodextrin is present in an amount effective for inhibiting the toxic effect of said agent.

9. The composition of claim 8 further comprising a pharmaceutically acceptable carrier or diluent.

10. The composition of claim 8 wherein said cyclodextrin of the formula cyclodextrin-[O—R] n is an alpha-, beta-, or gamma-cyclodextrin.

11. The composition of claim 8 wherein R is C 1-10 alkyl, such that the derivatized cyclodextrin is a hydroxyalkyl cyclodextrin.

12. The composition of claim 11 wherein the molar ratio of the gadolinium-based contrast agent to the hydroxyalkyl cyclodextrin is from 2:1 to about 10:1.