MRI image enhancement using complexes of paramagnetic cations and amine ligands containing a mixture of phosphonate and non-phosphonate pendant arms

A method of preferentially enhancing magnetic resonance image contrast in bone tissue and other tissue of a patient bearing recognition features in common with bone tissue, said method comprising administering to said patient an effective amount of a pharmaceutical agent comprising a physiologically compatible salt of the complex produced by the addition of a suitable paramagnetic metal cation to a chelator having the formula ##STR11## in which:

• t is 2 or 3;
• u is 2 or 3;
• v is 2 or 3;
• w is at least 2;
• at least two but not all of the R.sup.11 moieties are independently phosphonate-bearing groups of the formula ##STR12## in which R.sup.14, R.sup.15 and R.sup.16 are independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• R.sup.17 is selected from the group consisting of H, OH, NH.sub.2, and alkyl and aryl groups which do not interfere with complexation;
• and n is zero or 1;
• the R.sup.11 moieties which are not phosphonate-bearing groups are members independently selected from the group consisting of H, alkyl and aryl groups which do not interfere with complexation, and groups of the formula ##STR13## in which R.sup.14, R.sup.15, R.sup.16, R.sup.17, and n are as defined above, and R.sup.18 is a member
• selected from the group consisting of carboxyl, 2-hydroxy phenyl, and ##STR14## the R.sup.12 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• and
• the R.sup.13 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation.

A method of preferentially enhancing magnetic resonance image contrast, said method comprising administering to said patient an effective amount of a pharmaceutical agent comprising a physiologically compatible salt of the complex produced by the addition of a suitable paramagnetic metal cation to a chelator having the formula ##STR15## in which:

• at least three but not all of the R.sup.31 moieties are independently phosphonate-bearing groups of the formula ##STR16## in which R.sup.34, R.sup.35 and R.sup.36 are independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• R.sup.37 is selected from the group consisting of H, OH, NH.sub.2, and alkyl and aryl groups which do not interfere with complexation;
• and y is zero or 1;
• the R.sup.31 moieties which are not phosphonate-bearing groups are members independently selected from the group consisting of H, alkyl and aryl groups which do not interfere with complexation, and groups of the formula ##STR17## in which R.sup.34, R.sup.35, R.sup.36, R.sup.37 and y are as defined above, and R.sup.38 is a member selected from the group consisting of carboxyl, 2-hydroxy phenyl, and ##STR18## the R.sup.32 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• and
• the R.sup.33 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation.

A pharmaceutical agent comprising a physiologically compatible salt of a chelate of a paramagnetic metal cation and a compound having the formula ##STR19## in which:

• at least three but not all of the R.sup.31 moieties are independently phosphonate-bearing groups of the formula ##STR20## in which R.sup.34, R.sup.35 and R.sup.36 are independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• R.sup.37 is selected from the group consisting of H, OH, NH.sub.2, and alkyl and aryl groups which do not interfere with complexation;
• and y is zero or 1;
• the R.sup.31 moieties which are not phosphonate-bearing groups are members independently selected from the group consisting of H, alkyl and aryl groups which do not interfere with complexation, and groups of the formula ##STR21## in which R.sup.34, R.sup.35, R.sup.36, R.sup.37 and y are as defined above, and R.sup.38 is a member selected from the group consisting of carboxyl, 2-hydroxy phenyl, and ##STR22## the R.sup.32 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation;
• and
• the R.sup.33 moieties are each independently selected from the group consisting of H and alkyl and aryl groups which do not interfere with complexation.