Cyanine-containing compounds for cancer imaging and treatment

Abstract

This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.

1 . A compound having formula: 
       
         
           
           
               
               
           
         
       
       where X is selected from the group consisting of: hydrogen, halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, NHEt, SEt, S-Ph, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, and 4-S-Ph-NCS; q is 0 or 1; R 7  is selected from H and COOR 9 , where R 9  is H, CH 3 , or CH 2 CH 3 ; each R 1  is independently in each instance, (CH2)mR A , where m is an integer from 1 to 12, R A  is independently CH3, NH2, SH, COOH, SO3H, OH, halogen and CO—N-hydroxysuccinimide; each R 10  is independently in each instance selected from H, OH, OMe, halogen, NH 2 , NHR, NR 2  and COOH, where each R is independently C1-C6 alkyl; each R 3  is independently in each instance, selected from the group consisting of: methyl and phenyl. 
     
     
         2 . The compound of  claim 1 , wherein X is Cl and each R 3  is CH 3 . 
     
     
         3 . The compound of  claim 1 , wherein R 1  is (CH 2 ) m COOH and m is 1-6. 
     
     
         4 . The compound of  claim 1 , wherein R 1  is (CH 2 ) m SO 3 H and m is 1-6. 
     
     
         5 . The compound of  claim 1 , wherein R 1  is (CH 2 ) m CH 3  and m is 1-6. 
     
     
         6 . A compound having formula 
       
         
           
           
               
               
           
         
       
       where X is selected from the group consisting of: hydrogen, halogen, CN, Me, phenyl, OH, OMe, OPh, 4-O-Ph-NH 2 , 4-O-Ph-CH 2 CH 2 COOH, 4-O-Ph-CH 2 CH 2 CONHS, NH-Ph, NHEt, SEt, S-Ph, 4-S-Ph-COOH, 4-S-Ph-OH, 4-O-Ph-COOH, 4-O-Ph-NCS, and 4-S-Ph-NCS; q is 0 or 1; R 7  is selected from H and COOR 9 , where R 9  is H, CH 3 , or CH 2 CH 3 ; and CyR is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         7 . A method of imaging cancer cells comprising:
 introducing an imaging amount of a cyanine-containing compound of  claim 1  or  claim 6  to cancer cells,   exposing said cells to electromagnetic radiation; and   detecting light emission from the cyanine-containing compound.   
     
     
         8 . The method of  claim 7 , wherein the cells are present in vitro. 
     
     
         9 . The method of  claim 7 , wherein the cells are present in vivo. 
     
     
         10 . The method of  claim 7 , wherein the radiation is near infrared. 
     
     
         11 . The method of  claim 7 , wherein the compound is MHI-148, IR783, or IR780. 
     
     
         12 . The method of  claim 7 , wherein the cells are selected from lymphoma, Hodgkin's Disease, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, neuroblastoma/glioblastoma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancers, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, melanoma, colon cancer, and breast cancer. 
     
     
         13 . A method of treating cancer comprising:
 contacting cancer cells with a cytotoxic amount of a compound of  claim 1  or  6 .   
     
     
         14 . The method of  claim 13 , wherein the cells are present in vitro. 
     
     
         15 . The method of  claim 13 , wherein the cells are present in vivo. 
     
     
         16 . The method of  claim 13 , wherein the compound is MHI-148, IR783, or IR780. 
     
     
         17 . The method of  claim 13 , wherein the cells are selected from lymphoma, Hodgkin's Disease, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, neuroblastoma/glioblastoma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancers, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, melanoma, colon cancer, and breast cancer. 
     
     
         18 . A method of identifying cancer in a biological sample comprising: introducing an imaging amount of a cyanine-containing compound of  claim 1  or  6  to a biological sample;
 exposing the biological sample to excitation light; and 
 detecting the emission of light, wherein emission of light from the biological sample indicates cancer is present in the biological sample. 
 
     
     
         19 . The method of  claim 18 , wherein the tumor cells are circulating. 
     
     
         20 . The method of  claim 18 , wherein the biological sample is tissue. 
     
     
         21 . The method of  claim 18 , wherein the detecting step is performed using FACS, scanning microscopy, histochemical or immunohistochemical methods. 
     
     
         22 . The method of  claim 18 , wherein the biological sample is a biological fluid. 
     
     
         23 . The method of  claim 22 , wherein the biological fluid is selected from the group consisting of blood, a blood component, urine, saliva and body excretory materials. 
     
     
         24 . The method of  claim 18 , wherein the cells are present in vitro. 
     
     
         25 . The method of  claim 18 , wherein the cells are present in vivo. 
     
     
         26 . The method of  claim 18 , wherein the radiation is near infrared. 
     
     
         27 . The method of  claim 18 , wherein the compound is MHI-148, IR783, or IR780. 
     
     
         28 . The method of  claim 18 , wherein the compound is one of  claim 2 - 5 . 
     
     
         29 . The method of  claim 18 , wherein the cells are selected from lymphoma, Hodgkin's Disease, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, neuroblastoma/glioblastoma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancers, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, melanoma, colon cancer, and breast cancer. 
     
     
         30 . A pharmaceutical composition comprising a compound of  claim 1  to  6  and a pharmaceutically acceptable carrier.