Transition Metal Macrocyclics as MRI Contrast Agents for Molecular Imaging

A method of monitoring at least one of tissue temperature and pH in a patient in need thereof, the method comprising:

• administering to the patient a compound of Formula Ia or Formula IIa:
• wherein
• each of R10a, R11a, R12a, and R13a is independently selected from the group consisting of
• each of A and B is independently CR14aR15a;
• each G is independently CR20aR21a;
• each J is independently C or P(O−);
• each of R14a and R15a is independently selected from the group consisting of hydrogen, C1-C6 linear alkyl, and C3-C6 branched alkyl, wherein adjacent R14a and R15a groups may bond or fuse to form a C3-C12 cycloalkyl;
• each of R20a and R21a is independently selected from the group consisting of hydrogen, C1-C6 linear alkyl, and C3-C6 branched alkyl, wherein adjacent R20a and R21a groups may bond or fuse to form a C3-C12 cycloalkyl;
• X is a transition metal selected from the group consisting of Fe, Zn, Co, and Ni, Mn, Au, Pt, Cr, Pd, and Ti;
• and
• each occurrence of m, n, and q is independently an integer from 1-6;
• and
• measuring a change in the chemical shift of one or more protons in the compound.

A method of monitoring the efficacy of a cancer treatment in a patient in need thereof, the method comprising:

• administering to the patient a chemotherapy drug or pharmaceutical agent;
• administering to the patient, at the site of a tumor, a compound of Formula Ia or Formula IIa:
• wherein:
• each of R10a, R11a, R12a, and R13a is independently selected from the group consisting of
• each of A and B is independently CR14aR15a;
• each G is independently CR20aR21a;
• each J is independently C or P(O−);
• each of R14a and R15a is independently selected from the group consisting of hydrogen, C1-C6 linear alkyl, and C3-C6 branched alkyl, wherein adjacent R14a and R15a groups may bond or fuse to form a C3-C12 cycloalkyl;
• each of R20a and R21a is independently selected from the group consisting of hydrogen, C1-C6 linear alkyl, and C3-C6 branched alkyl, wherein adjacent R20a and R21a groups may bond or fuse to form a C3-C12 cycloalkyl;
• X is a transition metal selected from the group consisting of Fe, Zn, Co, and Ni, Mn, Au, Pt, Cr, Pd, and Ti;
• and
• each occurrence of m, n, and q is independently an integer from 1-6;
• and
• measuring a change in the chemical shift of one or more protons in the compound.