Mechanism-Based Targeted Pancreatic Beta Cell Imaging and Therapy

Abstract

Compositions for imaging pancreatic beta cells comprise chelator-antidiabetic agent conjugates and optionally chelated metals.

1 . A composition for imaging a pancreas comprising an antidiabetic agent, a chelator and a chelated metal ion. 
     
     
         2 . The composition of  claim 1 , wherein the metal ion is effective for contrast enhanced imaging when the composition is administered to a mammal during use. 
     
     
         3 . The composition of  claim 1 , wherein the chelator is diethylenetriamine pentaacetic acid (DTPA), ethylene diamine tetra-acetic acid (EDTA), cyclohexyl 1,2-diamine tetra-acetic acid (CDTA), ethyleneglycol-0, 0′bis (2-aminoethyl)-N,N,N′,N′-tetra-acetic acid (EGTA), N,N-bis(hydroxybenzyl)-ethylenediamine-N,N′-diacetic acid (HEED), triethylene tetramine hexa-acetic acid (TTHA), 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA), hydroxyethyldiamine triacetic acid (HEDTA), 1,4,8,11-tetra-azacyclo-tetradecane-N,N′,N″,N′″-tetra-acetic acid (TETA), dimercaptosuccinic acid (DMSA), triglycinbenzoyl thiol (MAG-3) and methylenebisphophonate (MDP). 
     
     
         4 . The composition of  claim 1 , wherein the chelator is DTPA. 
     
     
         5 . The composition of  claim 1 , wherein the antidiabetic agent binds preferentially to beta cells of the pancreas. 
     
     
         6 . The composition of  claim 1 , wherein the antidiabetic agent binds preferentially to the pancreatic beta cell sulphonylurea receptor SUR-1, angiotensin II receptor, or bradykinin receptor. 
     
     
         7 . The composition of  claim 1 , wherein the antidiabetic agent is nateglinide, glipizide, glyburide, or glimepiride. 
     
     
         8 . The composition of  claim 1 , wherein the metal ion is a radionuclide. 
     
     
         9 . The composition of  claim 1 , wherein the metal ion is a beta emitter. 
     
     
         10 . The composition of  claim 1 , wherein the metal ion is a gamma emitter. 
     
     
         11 . The composition of  claim 1 , wherein the metal ion is Tc-99m, Cu-60-64, Gd, Ho-166, or Re-187, 188. 
     
     
         12 . The composition of  claim 1 , further defined as  99m Tc-DTPA-nateglinide,  99m Tc-DTPA glipizide,  99m Tc-DTPA-glyburide or  99m Tc-DTPA-glimepiride. 
     
     
         13 . A method of treating a pancreatic disease comprising administering to a subject in need thereof a composition comprising an antidiabetic agent, a chelator and a chelated metal ion, wherein the metal ion is a beta emitter. 
     
     
         14 . The method of  claim 13 , wherein the chelated metal ion is  188 Re  90 Y or  166 Ho. 
     
     
         15 . The method of  claim 13 , wherein the pancreatic disease is diabetes, pancreatitis, hyperinsulinemia or insulinoma. 
     
     
         16 . A method of imaging a mammalian pancreas comprising administering to the mammal a composition comprising an antidiabetic agent, a chelator and a chelated metal ion, and detecting an image of the pancreas. 
     
     
         17 . The method of  claim 16 , wherein the image is a gamma image a PET image, or an MRI image. 
     
     
         18 . The method of  claim 16  wherein the composition comprises  99m Tc-DTPA-nateglinide. 
     
     
         19 - 38 . (canceled)