Method for monitoring blood flow and metabolic uptake in tissue with radiolabeled alkanoic acid

Abstract

The present invention relates to novel modified fatty acid analogs, where a positron or gamma-emitting label is placed at a position on a fatty acid backbone and an organic substituent is substituted at the 2,3; 3,4; 4,5; 5,6; and other sequence positions of a fatty acid backbone. These novel fatty acid analogs are designed to enter the tissues of interest by the same long chain fatty acid carrier mechanism as natural fatty acids, however, functional substituents in the 2,3; 3,4; 4,5; 5,6 and other sequence positions, block the catabolic pathway, thus trapping these analogs in a virtually unmodified form in the tissues of interest.

1 - 17 . (canceled) 
     
     
         18 . A radioactively labeled analog of a fatty acid that is taken up by mammalian tissue, comprising the formula: 
       
         
           
           
               
               
           
         
       
       wherein D is CH 2  or CH 2 CH 2 , E is CH 2  or CH 2 CH 2 , m is 0-10, n is 8-14 and R is CH 3 , aryl or a heterocyclic group, wherein cyclic organic substituent -CDCE- causes said analog to be metabolically trapped in said tissue. 
     
     
         19 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said organic substituent is bonded to the fatty acid analog at the C 2 , C 3 ; C 3 , C 4 ; C 4 , C 5 ; or C 5 , C 6  positions. 
     
     
         20 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said organic substituent causes said analog to be metabolically trapped in said tissue by permitting the occurrence of the first beta-oxidation step in which the carbon atom to which said substituent is bonded is beta to the carboxyl carbon atom, while preventing the cleaving off from said analog of the two carbon atoms to the right of the carbon atom to which said substituent is bonded. 
     
     
         21 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said tissue is heart tissue. 
     
     
         22 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said tissue is liver tissue. 
     
     
         23 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said tissue is tumor tissue. 
     
     
         24 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said analog emits detectable positrons after being taken up by said tissue. 
     
     
         25 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said analog emits detectable photons after being taken up by said tissue. 
     
     
         26 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein the carbon chain of said fatty acid is saturated. 
     
     
         27 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein the carbon chain of said fatty acid is unsaturated. 
     
     
         28 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said aryl group comprises a 5 to 7-membered ring structure. 
     
     
         29 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said heterocyclic group comprises a 3 to 5-membered ring structure. 
     
     
         30 . The radioactively labeled analog of a fatty acid of  claim 18 , wherein said radioactive isotope comprises  18 F,  123 I,  131 I,  34m Ci,  75 Br,  76 Br and  77 Br. 
     
     
         31 . The radioactively labeled analog of a fatty acid of  claim 30 , wherein said radioactive isotope of a halogen is bonded to a carbon atom on the straight chain of said analog. 
     
     
         32 - 119 . (canceled) 
     
     
         120 . The radioactively labeled analog of  claim 20 , wherein said organic substituent reduces metabolic dehydrogenation of said analog. 
     
     
         121 . The radioactively labeled analog of  claim 20 , wherein said organic substituent reduces metabolic hydroxylation of said analog. 
     
     
         122 - 146 . (canceled)