Use of texaphyrin in ocular diagnosis and therapy

Abstract

The use of texaphyrins for ocular diagnosis and therapy is provided, especially use of photosensitive texaphyrins for photodynamic therapy of conditions of the eye characterized by abnormal vasculature, such as macular degeneration, or pterygium, for example. The photosensitive texaphyrin may be a free-base texaphyrin or may be metallated with a diamagnetic metal. Preferably, the photosensitive texaphyrin is metallated with lutetium. Due to the dual wavelength absorption of texaphyrins, i.e., at 400-500 nm and at 700-800 nm, especially about 732 nm, as compared to porphyrins, texaphyrins are more effective and versatile for use in humans as compared to porphyrins. Texaphyrins serve as effective contrast agents in ocular angiography.

1 . A method for treating an ocular condition characterized by abnormal vasculature of a subject; the method of comprising: 
 administering a photosensitive texaphyrin to the subject; and    photoirradiating the vasculature.    
     
     
         2 . The method of  claim 1  wherein the photosensitive texaphyrin is fluorescent and the treating is further in combination with observing the ocular condition of the subject by observing fluorescence of the texaphyrin.  
     
     
         3 . The method of  claim 1  wherein the ocular condition is selected from the group consisting of macular degeneration, glaucoma, disc neovascularization, retinal neovascularization, pannus, pterygium, retinal neovasculature, choroidal neovasculature, ocular histoplasmosis syndrome, myopia, ocular inflammatory disease, central serous retinopathy, subretinal neovascular membrane, and neovasculature induced by neoplasm.  
     
     
         4 . The method of  claim 1  wherein the ocular condition of the subject is macular degeneration.  
     
     
         5 . The method of  claim 1  where the photosensitive texaphyrin has structure I:  
       
         
           
           
               
               
           
         
       
       or structure II:  
       
         
           
           
               
               
           
         
       
       wherein 
 M is a diamagnetic metal cation;  
 R 1 -R 4 , R 7  and R 8  are independently hydrogen, halide, hydroxyl, alkyl, alkenyl, alkynyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, hydroxyalkenyl, hydroxyalkynyl, saccharide, carboxy, carboxyalkyl, carboxyamide, carboxyamidealkyl, amino, aminoalkyl, a site-directing molecule, a catalytic group, or a couple that is coupled to a site-directing molecule or to a catalytic group;  
 R 6  and R 9  are independently selected from the groups of R 1 -R 4 , R 7  and R 8 , with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl;  
 R 5  and R 10 -R 12  are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, hydroxyalkyl, alkoxy, hydroxyalkoxy, hydroxyalkenyl, hydroxyalkynyl, carboxyalkyl, carboxyamide, carboxyamidealkyl, amino, aminoalkyl, or a couple that is coupled to a saccharide, to a site-directing molecule, or to a catalytic group;  
 R 13  is alkyl, alkenyl, oxyalkyl, or hydroxyalkyl having up to about 3 carbon atoms and having rotational flexibility around a first-bound carbon atom; and  
 n is an integer value less than or equal to 5.  
 
     
     
         6 . The method of  claim 1  wherein the photosensitive texaphyrin is selected from the group consisting of texaphyrins A1-A108 of Tables A and B.  
     
     
         7 . The method of  claim 1  wherein the photosensitive texaphyrin is bound to a diamagnetic metal cation and the diamagnetic metal cation is Lu(III), La(III), In(III), Zn(II) or Cd(II).  
     
     
         8 . The method of  claim 1  wherein the photosensitive texaphyrin is bound to a diamagnetic metal cation and the diamagnetic metal cation is Lu(III).  
     
     
         9 . The method of  claim 1  wherein the photoirradiating is with light having a wavelength range of about 700 to 800 nanometers.  
     
     
         10 . The method of  claim 1  wherein the photoirradiating is with light having a wavelength range of about 725-740 nanometers.  
     
     
         11 . The method of  claim 1  further comprising: 
 administering a paramagnetic texaphyrin to the subject, and  
 imaging the subject by magnetic resonance imaging.  
 
     
     
         12 . The method of  claim 1  wherein the photosensitive texaphyrin is LuT2BET.  
     
     
         13 . A method for observing vasculature in an eye of a subject, the method comprising: 
 administering a detectable texaphyrin to the subject; and    observing the vasculature of the eye.    
     
     
         14 . The method of  claim 13  where the detectable texaphyrin is fluorescent and the observing is by fluorescence.  
     
     
         15 . The method of  claim 14  where the fluorescent texaphyrin is in a metal complex with Y(III), Lu(III), or Gd(III).  
     
     
         16 . The method of  claim 14  where excitation light to induce fluorescence has a wavelength of about 400-500 nm.  
     
     
         17 . The method of  claim 14  where excitation light to induce fluorescence has a wavelength of about 700-800 nm.  
     
     
         18 . The method of  claim 13  where the detectable texaphyrin is complexed with a paramagnetic cation and the observing is by magnetic resonance imaging.  
     
     
         19 . The method of  claim 13  where the observing is by x-ray imaging.  
     
     
         20 . A method for photodynamic therapy of macular degeneration of a subject comprising: 
 administering a photosensitive texaphyrin to the subject; and    photoirradiating the macula.    
     
     
         21 . The method of  claim 20  where the photosensitive texaphyrin has structure I:  
       
         
           
           
               
               
           
         
       
       or structure II:  
       
         
           
           
               
               
           
         
       
       wherein 
 M is a diamagnetic metal cation;  
 R 1 -R 4 , R 7  and R 8  are independently hydrogen, halide, hydroxyl, alkyl, alkenyl, alkynyl, aryl, haloalkyl, nitro, formyl, acyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, hydroxyalkenyl, hydroxyalkeynl, saccharide, carboxy, carboxyalky, carboxyamide, carboxyamiodealkyl, amino, aminoalkyl, a site-directing molecule, a catalytic group, or a couple that is coupled to a site-directing molecule or to a catalytic group;  
 R 6  and R 9  are independently selected from the groups of R 1 -R 4 , R 7  and R 8 , with the proviso that the halide is other than iodide and the haloalkyl is other than iodoalkyl;  
 R 5  and R 10 -R 12  are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, hydroxyalkyl, alkoxy, hydroxyalkoxy, hydroxyalkenyl, hydroxyalkynyl, carboxyalkyl, carboxyamide, carboxyamidealkyl, amino, aminoalkyl, or a couple that is coupled to a saccharide, to a site-directing molecule, or to a catalytic group;  
 R 13  is alkyl, alkenyl, oxyalkyl, or hydroxyalkyl having up to about 3 carbon atoms and having rotational flexibility around a first-bound carbon atom; and  
 n is an integer value less than or equal to 5.  
 
     
     
         22 . The method of  claim 21  wherein the photosensitive texaphyrin is selected from the group consisting of texaphyrins A1-A108 of Tables A and B.  
     
     
         23 . The method of  claim 21  wherein the photosensitive texaphyrin is bound to a diamagnetic metal cation and the diamagnetic metal cation is Lu(III), La(III), In(III), Zn(II) or Cd(II).  
     
     
         24 . The method of  claim 21  wherein the photosensitive texaphyrin is bound to a diamagnetic metal cation and the diamagnetic metal cation is Lu(III).  
     
     
         25 . A method for observing and treating an ocular condition characterized by abnormal vasculature of a subject using a single agent, the method comprising: 
 administering a photosensitive fluorescent texaphyrin to the subject; observing the ocular condition of the subject by fluorescence of the texaphyrin; and photoirradiating the vasculature.    
     
     
         26 . The method of  claim 5  wherein the photosensitive texaphyrin has structure I.  
     
     
         27 . The method of  claim 26  wherein: R 1 -R 4 , R 7  and R 8  are independently alkyl, hydroxyalkyl, or hydroxyalkoxy; and R 5 , R 6  and R 9 -R 12  are hydrogen.  
     
     
         28 . The method of  claim 27  wherein R 1  is hydroxyalkyl; and R 2 , R 3  and R 4  are alkyl.  
     
     
         29 . The method of  claim 1  wherein the photosensitive texaphyrin is administered by rapid infusion as a bolus.  
     
     
         30 . The method of  claim 29  comprising administering 0.01 to 5 μmol/kg of the photosensitive texaphyrin in a sterile aqueous or aqueous propylene glycol solution.  
     
     
         31 . The method of  claim 30  wherein the photosensitive texaphyrin is LuT2BET.  
     
     
         32 . The method of  claim 21  wherein the photosensitive texaphyrin has structure I.  
     
     
         33 . The method of  claim 32  wherein: R 1 -R 4 , R 7  and R 8  are independently alkyl, hydroxyalkyl, or hydroxyalkoxy; and R 5 , R 6  and R 9 -R 12  are hydrogen.  
     
     
         34 . The method of  claim 33  wherein R 1  is hydroxyalkyl; and R 2 , R 3  and R 4  are alkyl.  
     
     
         35 . The method of  claim 21  wherein the photosensitive texaphyrin is administered by rapid infusion as a bolus.  
     
     
         36 . The method of  claim 35  comprising administering 0.01 to 5 μmol/kg of the photosensitive texaphyrin in a sterile aqueous or aqueous propylene glycol solution.  
     
     
         37 . The method of  claim 36  wherein the photosensitive texaphyrin is LuT2BET.