Methods of MRI enhancement using compounds having improved functionalization
First Claim
1. A method of magnetic resonance image enhancement in a subject, the method comprising:
- administering to the subject an effective amount of a texaphyrin; and
imaging the subject using a magnetic resonance device;
wherein the texaphyrin has structure;
##STR14## wherein M is a paramagnetic metal cation;
R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule,a catalytic group, or a couple to a site-directing molecule or to a catalytic group;
R6 and R9 are independently selected from the groups of R1 -R4, R7 and R8, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl;
R5 and R10 -R12 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a saccharide, to a site-directing molecule or to a catalytic group;
at least one of R5, R6, R9, R10, R11 and R12 is other than hydrogen; and
Z is an integer less than or equal to 5.
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Abstract
Texaphyrin metal complexes having improved functionalization include the addition of electron-donating groups to positions 2, 7, 12, 15, 18 and/or 21 and/or the addition of electron-withdrawing groups to positions 15 and/or 18 of the macrocycle. Electron-donating groups at positions 2, 7, 12, 15, 18 and/or 21 contribute electrons to the aromatic π system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis. These texaphyrin metal complexes having enhanced stability are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic therapy, RNA hydrolysis, DNA photocleavage, and applications requiring singlet oxygen production for cytotoxicity. Electron-withdrawing groups at positions 15 and/or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential are useful for radiation sensitization applications.
64 Citations
16 Claims
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1. A method of magnetic resonance image enhancement in a subject, the method comprising:
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administering to the subject an effective amount of a texaphyrin; and imaging the subject using a magnetic resonance device; wherein the texaphyrin has structure;
##STR14## wherein M is a paramagnetic metal cation;R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, a catalytic group, or a couple to a site-directing molecule or to a catalytic group; R6 and R9 are independently selected from the groups of R1 -R4, R7 and R8, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl; R5 and R10 -R12 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a saccharide, to a site-directing molecule or to a catalytic group; at least one of R5, R6, R9, R10, R11 and R12 is other than hydrogen; and Z is an integer less than or equal to 5. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method of detection of neoplastic tissue in a subject, the method comprising:
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administering to the subject a texaphyrin in an amount effective to enhance a magnetic resonance image of neoplastic tissue; and detecting neoplastic tissue by magnetic resonance imaging of the subject; wherein the texaphyrin has structure;
##STR15## wherein M is a paramagnetic metal cation;R1 -R4, R7 and R8 are independently hydrogen, halide, hydroxyl, alkyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, a catalytic group, or a couple to a site-directing molecule or to a catalytic group; R6 and R9 are independently selected from the groups of R1 -R4, R7 and R8, with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl; R5 and R10 -R12 are independently hydrogen, alkyl, aryI, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a saccharide, to a site-directing molecule or to a catalytic group; at least one of R5, R6, R9, R10, R11 and R12 is other than hydrogen; and Z is an integer less than or equal to 5. - View Dependent Claims (16)
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Specification