US2009162281A1PendingUtilityA1

Radionuclide labeling of Vitamin B12 and Co-enzymes thereof

Individually held — no corporate assignee on recordPriority: Nov 13, 1995Filed: Nov 4, 2008Published: Jun 25, 2009
Est. expiryNov 13, 2015(expired)· nominal 20-yr term from priority
A61K 41/0095A61K 51/04A61P 35/00C07H 23/00A61K 51/0497
74
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Claims

Abstract

A compound useful for in vivo imaging of organs and tumors is provided of formula: wherein is a cobalamin, is derived from a corrin carboxylic acid group of said cobalamin, Y is a linking group and X is a chelating group, optionally comprising a detectable radionuclide or a paramagnetic metal ion, and n is 1-3.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutically acceptable salt of compound of the formula: 
     
       
         
         
             
             
         
       
       wherein the moiety 
     
     
       
         
         
             
             
         
       
       is cobalamin, 
     
     
       
         
         
             
             
         
       
       is a b-, d-, or e-carboxy residue of cobalamin; X is CN, OH, methyl, or adenosyl; Y is a linking group; and DET is independently selected from a chelating group comprising a radionuclide and a chelating group comprising a paramagnetic metal ion. 
     
   
   
       2 . The compound of  claim 1 , wherein C(═O) is the b-carboxy residue of cobalamin. 
   
   
       3 . The compound of  claim 1 , wherein C(═O) is the d-carboxy residue of cobalamin. 
   
   
       4 . The compound of  claim 1 , wherein each DET is a chelating group comprising a radionuclide. 
   
   
       5 . The compound of  claim 4 , wherein each radionuclide is independently selected from Antimony-124, Antimony-125, Arsenic-74, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115, Cadmium-115m, Calcium-45, Cerium-139, Cerium-141, Cerium-144, Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Erbium-169, Europium-152, Gadolinium-153, Gold-195, Gold-199, Hafnium-175, Hafnium-175-181, Indium-111, Iridium-192, Iron-55, Iron-59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103, Platinum-195m, Praseodymium-143, Promethium-147, Protactinium-233, Radium-226, Rhenium-186, Rhenium-188, Rubidium-86, Ruthenium-103, Ruthenium-106, Scandium-44, Scandium-46, Selenium-75, Silver-10m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium-204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65, and Zirconium-95. 
   
   
       6 . The compound of  claim 5 , wherein each radionuclide is independently selected from In 111 , Yt 90 , Tc 99 , Gd 153 , and Re 186 . 
   
   
       7 . The compound of  claim 1 , wherein each chelating group is independently selected from EDTA, DTPA, DOTA, TETA, and DCTA. 
   
   
       8 . The compound of  claim 7 , wherein each chelating group is DTPA. 
   
   
       9 . The compound of  claim 1 , wherein each Y is independently selected from a divalent monomer, dimer, and trimer of —N(H)(CH 2 ) 2-6 N(H)—. 
   
   
       10 . The compound of  claim 9 , wherein each Y is —N(H)(CH 2 ) 4 N(H)—. 
   
   
       11 . A diagnostic or therapeutic unit dose form comprising a compound of the formula: 
     
       
         
         
             
             
         
       
     
     wherein the moiety 
     
       
         
         
             
             
         
       
     
     is cobalamin, 
     
       
         
         
             
             
         
       
     
     is a b-, d-, or e-carboxy residue of cobalamin; X is CN, OH, methyl, or adenosyl; Y is a linking group; and DET is independently selected from a chelating group comprising a radionuclide and a chelating group comprising a paramagnetic metal ion; or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable vehicle. 
   
   
       12 . The unit dose form of  claim 11 , wherein C(═O) is the b-carboxy residue of cobalamin. 
   
   
       13 . The unit dose form of  claim 11 , wherein C(═O) is the d-carboxy residue of cobalamin. 
   
   
       14 . The unit dose form of  claim 11 , wherein each DET is a chelating group comprising a radionuclide. 
   
   
       15 . The unit dose form of  claim 14 , wherein each radionuclide is independently selected from Antimony-124, Antimony-125, Arsenic-74, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115, Cadmium-15m, Calcium-45, Cerium-139, Cerium-141, Cerium-144, Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Erbium-169, Europium-152, Gadolinium-153, Gold-195, Gold-199, Hafnium-175, Hafnium-175-181, Indium-111, Iridium-192, Iron-55, Iron-59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103, Platinum-195m, Praseodymium-143, Promethium-147, Protactinium-233, Radium-226, Rhenium-186, Rhenium-188, Rubidium-86, Ruthenium-103, Ruthenium-106, Scandium-44, Scandium-46, Selenium-75, Silver-110m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium-204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65, and Zirconium-95. 
   
   
       16 . The unit dose form of  claim 11 , wherein each radionuclide is independently selected from In 111 , Yt 90 , Tc 99  Gd 153  and Re 186 . 
   
   
       17 . The unit dose form of  claim 11 , wherein each chelating group is independently selected from EDTA, DTPA, DOTA, TETA, and DCTA. 
   
   
       18 . The unit dose form of  claim 17 , wherein each chelating group is DTPA. 
   
   
       19 . The unit dose form of  claim 11 , wherein each Y is independently selected from a divalent monomer, dimer, and trimer of —N(H)(CH 2 ) 2-6 N(H)—. 
   
   
       20 . The unit dose form of  claim 19 , wherein each Y is —N(H)(CH 2 ) 4 N(H)—. 
   
   
       21 . The unit dose form of  claim 11 , formulated for parenteral administration. 
   
   
       22 . The unit dose form of  claim 11 , formulated for intravenous administration. 
   
   
       23 . The unit dose form of  claim 11 , formulated for intravenous administration. 
   
   
       24 . The unit dose form of  claim 11 , formulated for intraperitoneal administration. 
   
   
       25 . The unit dose form of  claim 11 , formulated for oral administration. 
   
   
       26 . The unit dose form of  claim 11 , wherein the pharmaceutically acceptable vehicle is saline.

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