DTPA monoamides for MRI

A method of X-ray imaging comprising imaging a patient to whom a contrast agent has been administered, the improvement wherein said contrast agent is a physiologically acceptable chelate compound of formula I ##STR7## wherein Z.sup.1 and Z.sup.2 are each independently H or --(CH.sub.2).sub.m --(C.sub.6 H.sub.4).sub.q --(O).sub.k --(CH.sub.2).sub.n --(C.sub.6 H.sub.4).sub.l --(O).sub.r --R,

• m and n are each independently 0-20,
• k, l, q and r are each independently 0 or 1, and
• R is H, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl substituted by OR.sup.1, or CH.sub.2 COOR.sup.1,
• R.sup.1 is H, C.sub.1 -C.sub.6 -alkyl, or benzyl,
• R.sup.2 is a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-atoms which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• R.sup.3 is H or a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-atoms, which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• X is H and/or a metal ion equivalent of an element of atomic numbers 21-29, 31, 32, 37-40, 42-44, 49 or 57-83, wherein acid groups are, in each case, optionally present as an ester with C.sub.1 -C.sub.6 -alkyl, benzyl or 4-methoxybenzyl, or as an amide wherein the nitrogen atom of said amide is substituted by at least one saturated or unsaturated straight-chain, branched-chain or cyclic hydrocarbon radical with up to 5 C atoms, wherein said at least one hydrocarbon radical is optionally substituted by 1-3 hydroxy groups and/or 1-3 C.sub.1 -C.sub.4 -hydroxy groups, or said amide is in the form of a 5- or 6-membered heterocyclic ring with inclusion of the amide nitrogen atom;
• or
• a salt thereof with an inorganic and/or organic base, an amino acid or an amino acid amide,
• wherein at least two of substituents X are metal ion equivalents of at least one element of atomic numbers 21-29, 42, 44 or 57-83, at least one of substituents Z.sup.1 and Z.sup.2 is H, and, if n and l are each 0, then k and r are not both 1.

A method of radiodiagnostic imaging comprising imaging a patient to whom a contrast agent has been administered, the improvement wherein said contrast agent is a physiologically acceptable chelate compound of formula I ##STR8## wherein Z.sup.1 and Z.sup.2 are each, independently, H or --(CH.sub.2).sub.m --(C.sub.6 H.sub.4).sub.q --(O).sub.k --(CH.sub.2).sub.n --(C.sub.6 H.sub.4).sub.l --(O).sub.r --R,

• m and n are each independently 0-20,
• k, l, q and r are each independently 0 or 1, and
• R is H, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl substituted by OR.sup.1, or CH.sub.2 COOR.sup.1,
• R.sup.1 is H, C.sub.1 -C.sub.6 -allyl, or benzyl,
• R.sup.2 is a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-atoms which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• R.sup.3 is H or a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-ators, which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• X is H and/or a metal ion equivalent of a radionuclide of atomic numbers 27, 29, 31, 32, 37-39, 43, 49, 62, 64, 70 or 77 wherein acid groups are, in each case, optionally present as an ester with C.sub.1 -C.sub.6 -alkyl, benzyl or 4-methoxybenzyl, or as an amide wherein the nitrogen atom of said amide is substituted by at least one saturated or unsaturated straight-chain, branched-chain or cyclic hydrocarbon radical with up to 5 C atoms, wherein said at least one hydrocarbon radical is optionally substituted by 1-3 hydroxy groups and/or 1-3 C.sub.1 -C.sub.4 -hydroxy groups, or said amide is in the form of a 5- or 6-membered heterocyclic ring with inclusion of the amide nitrogen atom;
• or
• a salt thereof with an inorganic and/or organic base, an amino acid or an amino acid amide,
• wherein at least one of substituents Z.sup.1 and Z.sup.2 is H, and, if n and l are each 0, then k and r are not both 1.

In a method of radiation therapy comprising administering a radiotherapeutic agent to a patient, the improvement wherein said agent is a physiologically acceptable chelate compound of formula I ##STR9## wherein Z.sup.1 and Z.sup.2 are each independently H or --(CH.sub.2).sub.m --(C.sub.6 H.sub.4).sub.q --(O).sub.k --(CH.sub.2).sub.n --(C.sub.6 H.sub.4).sub.l --(O).sub.r --R,

• m and n are each independently 0-20,
• k, l, q and r are each independently 0 or 1, and
• R is H, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl substituted by OR.sup.1, or CH.sub.2 COOR.sup.1,
• R.sup.1 is H, C.sub.1 -C.sub.6 -alkyl, or benzyl,
• R.sup.2 is a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-atoms which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• R.sup.3 is H or a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C-atoms, which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C-atoms which is optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C-atoms optionally substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• X is H and/or a metal ion equivalent of an element of atomic numbers 21-29, 31, 32, 37-40, 42-44, 49 or 57-83, wherein acid groups are, in each case, optionally present as an ester with C.sub.1 -C.sub.6 -alkyl, benzyl or 4-methoxybenzyl, or as an amide wherein the nitrogen atom of said amide is substituted by at least one saturated or unsaturated straight-chain, branched-chain or cyclic hydrocarbon radical with up to 5 C atoms, wherein said at least one hydrocarbon radical is optionally substituted by 1-3 hydroxy groups and/or 1-3 C.sub.1 -C.sub.4 -hydroxy groups, or said amide is in the form of a 5- or 6-membered heterocyclic ring with inclusion of the amide nitrogen atom;
• or
• a salt thereof with an inorganic and/or organic base, an amino acid or an amino acid amide,
• wherein at least one radionuclide is an element of atomic numbers 27, 29, 31, 32, 37-39, 43, 49, 62, 64, 70 or 77, at least one of substituents Z.sup.1 and Z.sup.2 is H, and, if n and l are each 0, then k and r are not both 1.

In a method of NMR imaging comprising imaging a patient to whom a contrast agent has been administered, the improvement wherein:

• the patient's gastrointestinal tract, renal system, and/or hepatobiliary system is imaged, and
• said contrast agent is a physiologically acceptable chelate compound of formula ##STR10## wherein Z.sup.1 and Z.sup.2 are each, independently, H or --(CH.sub.2).sub.m --(C.sub.6 H.sub.4).sub.q --(O).sub.k --(CH.sub.2).sub.n --(C.sub.6 H.sub.4).sub.l --(O).sub.r --R,
• m and n are each independently 0-20,
• k, l, q and r are each independently 0 or 1, and
• R is H, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl substituted by OR.sup.1, or CH.sub.2 COOR.sup.1,
• R.sup.1 is H, C.sub.1 -C.sub.6 -alkyl, or benzyl,
• R.sup.2 is a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C atoms which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• R.sup.3 is H or a saturated, unsaturated, straight-chain or branched-chain or cyclic non-aromatic hydrocarbyl group with up to 20 C atoms, which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• an aryl group of up to 10 C atoms which is substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or
• an aralkyl group of up to 16 C atoms substituted by a carboxyl group, a sulfone group, a carboxyl group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl, or a sulfone group esterified with C.sub.1 -C.sub.6 -alkyl or benzyl,
• X is H and/or a metal ion equivalent of an element of atomic numbers 21-29, 31, 32, 37-40, 42-44, 49 or 57-83, wherein acid groups are, in each case, optionally present as an ester, or as an amide;
• a salt thereof with an inorganic and/or organic base, an amino acid or an amino acid amide,
• wherein at least two of substituents X are metal ion equivalents of at least one element of atomic numbers 21-29, 42, 44 or 58-70, at least one of substituents Z.sup.1 and Z.sup.2 is H, and, if n and l are each 0, then k and r are not both 1.