Patient selection method for inflammation

Abstract

The invention relates to methods and compositions for the selection of patients for therapy with an anti-inflammatory drug. More particularly, the invention relates to compositions comprising folate-imaging agent conjugates for the selection of patients for therapy with an anti-inflammatory drug, and methods and uses therefor.

What is claimed is: 
     
         1 . A method for selecting a patient for therapy with an anti-inflammatory drug, the method comprising the step of
 administering to the patient a folate-imaging agent conjugate, wherein the folate-imaging agent conjugate is used to predict the response of the patient to the anti-inflammatory drug.   
     
     
         2 . The method of  claim 1  wherein the folate-imaging agent conjugate produces a detectable signal in the patient, wherein the signal is detected, and wherein the detection of the signal is used to predict the response of the patient to the anti-inflammatory drug. 
     
     
         3 . The method of  claim 2  wherein the signal is a radioactive signal. 
     
     
         4 . The method of  claim 2  wherein the signal is produced by a chromophore. 
     
     
         5 . The method of  claim 4  wherein the chromophore is a fluorophore. 
     
     
         6 . The method of  claim 5  wherein the fluorophore is selected from the group consisting of a fluorescein, a rhodamine, a phycoerythrin, a long wavelength fluorescent dye, and a cyanine. 
     
     
         7 . The method of  claim 2  wherein the signal is produced as a result of binding of the folate-imaging agent conjugate to activated macrophages. 
     
     
         8 . The method of  claim 1  wherein the administering step comprises a first administering step and a second administering step. 
     
     
         9 . The method of  claim 8  wherein the first and second administering steps produce a first signal and a second signal, respectively. 
     
     
         10 . The method of  claim 9  wherein the first signal and the second signal are quantified. 
     
     
         11 . The method of  claim 9  wherein the first signal is obtained by administering the folate-imaging agent conjugate prior to administration of the anti-inflammatory drug. 
     
     
         12 . The method of  claim 9  wherein the first signal is obtained by administering the folate-imaging agent conjugate on the same day as treatment with the anti-inflammatory drug is initiated. 
     
     
         13 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate subsequent to the administration of the anti-inflammatory drug. 
     
     
         14 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate within about 21 days after administration of the anti-inflammatory drug is initiated. 
     
     
         15 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate within about 1 week, about 2 weeks, about 3 weeks, or about 4 weeks after the administration of the anti-inflammatory drug is initiated. 
     
     
         16 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate on any one of the days within about 21 days after the administration of the anti-inflammatory drug is initiated. 
     
     
         17 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate on any one of the days within about 12 weeks after the administration of the anti-inflammatory drug is initiated. 
     
     
         18 . The method of  claim 9  wherein the second signal is reduced by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the first signal, and wherein the reduction indicates that the patient should continue to be treated with the anti-inflammatory drug. 
     
     
         19 . The method of  claim 9  wherein the second signal is obtained by administering the folate-imaging agent conjugate about 2, about 3, about 4, about 5, about 6, about 12, about 15, or about 21 days after the administration of the anti-inflammatory drug is initiated. 
     
     
         20 . The method of  claim 1  wherein the inflammatory disease is selected from the group consisting of arthritis, osteoarthritis, rheumatoid arthritis, atherosclerosis, psoriasis, ischemia/reperfusion injury, pulmonary fibrosis, organ transplant rejection, ulcerative colitis, impact trauma, osteomyelitis, multiple sclerosis, scleroderma, Crohn's disease, Sjögren's syndrome, glomerulonephritis, systemic sclerosis, sarcoidosis, an inflammatory lesion, and chronic inflammation. 
     
     
         21 . The method of  claim 9  wherein the folate-imaging agent conjugate has the formula 
       
         
           
           
               
               
           
         
       
       wherein M is a radionuclide. 
     
     
         22 . The method of  claim 21 , wherein the radionuclide is selected from the group consisting of an isotope of gallium, an isotope of indium, an isotope of copper, an isotope of technetium, and an isotope of rhenium. 
     
     
         23 . The method of  claim 22  wherein the radionuclide is an isotope of technetium. 
     
     
         24 . The method of  claim 23  wherein the technetium is  99m -technetium. 
     
     
         25 . The method of  claim 1  wherein the folate-imaging agent conjugate is  99m Tc-EC20.