MRI image enhancement compositions

A pharmaceutical composition comprising an MRI agent having the formula selected from the group consisting of:

• 31
• iv) and mixtures thereof;
• wherein each R is independently selected from the group consisting of:
• i) C1—C18 hydrocarbyl;
• ii) —(CH2)nCO2—;
• iii) CH3(CH2)nCO—;
• iv) —(CH2)nR1;
• v) —(CH2)nOPO3—;
• vi) —[(CH2)nOPO3R2(phenyl)2]—;
• R1 is hydroxyl, 2-hydroxyphenyl, 2-pyridyl, 2-furfuryl, and mixtures thereof;
• R2 is C1—C12 linear, branched, or cyclic alkylene;
• R3 is selected from the group consisting of:
• i) hydrogen;
• ii) C1—C18 hydrocarbyl;
• iii) —OH;
• iv) —(CH2)mCO2—;
• v) —O(CH2)mCO2—;
• vi) and mixtures thereof;
• the indices m and n have the value from 0 to about 10;
• X is an pharmaceutically compatible anion in sufficient amount q to provide electronic neutrality.

A method for providing an enhanced magnetic resonance image contrast in human or animal tissue, said method comprising the step of administering to a human an effective amount, of a composition comprising:

• a) from about 0.01% to about 99.99% by weight, of a 1,4,8,11 -tetraaza-bicyclo[6.6.2] hexadecane manganese (II) complex magnetic resonance imaging agent selected from the group:
• 32
• iv) and mixtures thereof;
• wherein each R is independently selected from the group consisting of:
• i) C1—C18 hydrocarbyl;
• ii) —(CH2)nCO2—;
• iii) CH3(CH2)nCO—;
• iv) —(CH2)nR1;
• v) —(CH2)nOPO3—;
• vi) —[(CH2)nOPO3R2(phenyl)2]—;
• R1 is hydroxyl, 2-hydroxyphenyl, 2-pyridyl, 2-furfuryl, and mixtures thereof;
• R2 is C1—C12 linear, branched, or cyclic alkylene;
• R3is selected from the group consisting of:
• i) hydrogen;
• ii) C1—C18 hydrocarbyl;
• iii) —OH;
• iv) —(CH2)mCO2—;
• v) —O(CH2)mCO2—;
• vi) and mixtures thereof;
• the indices m and n have the value from 0 to about 10;
• X is an pharmaceutically compatible anion in sufficient amount q to provide electronic neutrality;
• and
• b) the balance carriers and other adjunct ingredients.

A method for providing an enhanced magnetic resonance image contrast in human or animal tissue, said method comprising the step of:

• A) administering to a human an effective amount of a composition comprising:
• a) from about 0.01% to about 99.99% by weight, of a 1,4,8,11-tetraaza-bicyclo[6.6.2] hexadecane manganese (II) complex magnetic resonance imaging agent selected from the group:
• 33
• iv) and mixtures thereof;
• wherein each R is independently selected from the group consisting of:
• i) C1—C18 hydrocarbyl;
• ii) —(CH2)nCO2—;
• iii) CH3(CH2)nCO—;
• iv) —(CH2)nR1;
• v) —(CH2)nOPO3—;
• vi) —[(CH2)nOPO3R2(phenyl)2]—;
• R1 is hydroxyl, 2-hydroxyphenyl, 2-pyridyl, 2-furfuryl, and mixtures thereof;
• R2 is C1—C12 linear, branched, or cyclic alkylene;
• R3 is selected from the group consisting of:
• i) hydrogen;
• ii) C2—C18 hydrocarbyl;
• iii) —OH;
• iv) —(CH2)mCO2—;
• v) —O(CH2)mCO2—;
• vi) and mixtures thereof;
• the indices m and n have the value from 0 to about 10;
• X is an pharmaceutically compatible anion in sufficient amount q to provide electronic neutrality;
• and
• b) the balance carriers and other adjunct ingredients;
• and
• B) sustaining said effective amount of MRI agent for a period of time exceeding one hour.