Tumor imaging and treatment by water soluble texaphyrin metal complexes
First Claim
1. A method of treating a host harboring atheroma, leukemia., lymphoma, sarcoma, or carcinoma comprising:
- administering to the host as a first agent a water soluble hydroxy-substituted texaphyrin having structure (A);
##STR12## wherein M is a detectable metal;
R1, R2, R3, R4, and R5 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxyalkyl or carboxyamidealkyl where at least one of R1, R2, R3, R4, and R5 is hydroxyl, oxyhydroxyalkyl, saccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl;
the molecular weight of any one of R1, R2, R3, R4, or R5 is less than or equal to about 1000 daltons;
N is an integer less than or equal to 2;
determining localization sites in the host by reference to the detectable metal;
administering to the host as a second agent a water soluble hydroxy-substituted texaphyrin having structure (A) wherein M is a diamagnetic metal, and R1, R2, R3, R4, R5, the molecular weight and N are as described above; and
photoirradiating the second agent in proximity to said atheroma, leukemia, lymphoma, sarcoma, or carcinoma.
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Accused Products
Abstract
The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
63 Citations
24 Claims
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1. A method of treating a host harboring atheroma, leukemia., lymphoma, sarcoma, or carcinoma comprising:
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administering to the host as a first agent a water soluble hydroxy-substituted texaphyrin having structure (A);
##STR12## wherein M is a detectable metal;R1, R2, R3, R4, and R5 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxyalkyl or carboxyamidealkyl where at least one of R1, R2, R3, R4, and R5 is hydroxyl, oxyhydroxyalkyl, saccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl; the molecular weight of any one of R1, R2, R3, R4, or R5 is less than or equal to about 1000 daltons; N is an integer less than or equal to 2; determining localization sites in the host by reference to the detectable metal; administering to the host as a second agent a water soluble hydroxy-substituted texaphyrin having structure (A) wherein M is a diamagnetic metal, and R1, R2, R3, R4, R5, the molecular weight and N are as described above; and photoirradiating the second agent in proximity to said atheroma, leukemia, lymphoma, sarcoma, or carcinoma. - View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23)
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2. A method of treating a host harboring leukemia, lymphoma, sarcoma, or carcinoma comprising:
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administering to the host an effective amount of a water soluble hydroxy-substituted texaphyrin having structure (A);
##STR13## wherein;
M is a diamagnetic metal;R1, R2, R3, R4, and R5 are independently hydrogen, hydroxyl, alkyl hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxyalkyl or carboxyamidealkyl where at least one of R1, R2, R3, R4, and R5 is hydroxyl, oxyhydroxyalkyl, saccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl; the molecular weight of any one of R1, R2, R3, R4, or R5 is less than or equal to about 1000 daltons; N is an integer less than or equal to 2; and photoirradiating the water soluble hydroxy-substituted texaphyrin in proximity to the leukemia, lymphoma, sarcoma, or carcinoma. - View Dependent Claims (18, 24)
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3. A method of treating a host harboring atheroma, leukemia, lymphoma, sarcoma, or carcinoma comprising:
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administering to the host as a first agent a water soluble hydroxy-substituted texaphyrin having structure (A);
##STR14## wherein;
M is a detectable metal;R1, R2, R3, R4, and R5 are independently H, OH, Cn H.sub.(2n+1) OY or OCn H.sub.(2n+1) Oy where at least one of R1, R2, R3, R4, and R5 is Cn H.sub.(2n+1) OY or OCn H.sub.(2n+1) Oy, having at least one hydroxy substituent; the molecular weight of any one of R1, R2, R3, R4, or R5 is less than or equal to about 1000 daltons; n is a positive integer from 1 to 10; y is zero or a positive integer less than or equal to (2n+1); N is an integer less than or equal to 2;
determining localization sites in the host by reference to thedetectable metal;
administering to the host as a second agent a water solublehydroxy-substituted texaphyrin having structure (A) wherein M is a diamagnetic metal, and R1, R2, R3, R4, R5, the molecular weight and N are as described above; and photoirradiating the second agent in proximity to said atheroma, leukemia, lymphoma, sarcoma, or carcinoma.
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4. A method of treating a host harboring atheroma comprising:
administering to the host an effective amount of a water soluble hydroxy-substituted texaphyrin having structure (A);
##STR15## wherein;
M is a diamagnetic metal;R1, R2, R3, R4, and R5 are independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, carboxyalkyl or carboxyamidealkyl where at least one of R1, R2, R3, R4, and R5 is hydroxyl, oxyhydroxyalkyl, saccharide, oxyalkyl, carboxyalkyl, carboxyamidealkyl or hydroxyalkyl; the molecular weight of any one of R1, R2, R3, R4, or R5 is less than or equal to about 1000 daltons; N is an integer less than or equal to 2; and
photoirradiating the water soluble hydroxy-substituted texaphyrin in proximity to the atheroma.
Specification