F-18 Labeled Amino Acid Analogs

Abstract

The present invention relates to Halogenated amino acid analogues for use in diagnosis, which compounds have the general formula wherein: R is (C 1 -C 6 )alkyl optionally substituted with thioether or ether oxygen atom when n=0, or a substituted aromatic or heteraromatic ring when n=1-6; and m=0 or 1; and X is a halogen atom. The invention further relates to precursor compounds for these analogues, to a method of preparing these analogues, to a pharmaceutical composition comprising these analogues and to the use of these analogues and compositions in the diagnosis of cancer.

1 . A halogenated amino acid analogue having the general formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 X is a radioactive halogen;  
 m is  0  or  1 ; and  
 R is (C 1 -C 6 ) alkyl optionally substituted with thioether or ether oxygen atom.  
 
     
     
         2 . The analogue of  claim 1 , wherein R is methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl or methyl thioethyl.  
     
     
         3 - 4 . (canceled)  
     
     
         5 . The analogue of claim  4 , wherein the halogen is  18 F.  
     
     
         6 . The analogue of claim  4 , wherein the halogen is  123 I.  
     
     
         7 - 8 . (canceled)  
     
     
         9 . The analogue of  claim 1 , wherein the analogue is selected from the group consisting of: [ 18 F] labeled alanine; [ 18 F] labeled valine; [ 18 F] labeled leucine; [ 18 F] labeled isoleucine; and [ 18 F] labeled methionine.  
     
     
         10 . A pharmaceutical composition comprising the analogue of  claim 1  and at least one of an excipient, carrier and diluent.  
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition is used as a tracer in at least one of Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (MRI).  
     
     
         12 - 13 . (canceled)  
     
     
         14 . A method for diagnosing a patient for the presence of tumors and/or metastases, the method comprising: 
 administering a diagnostically effective amount of the analogue of  claim 1  into the body of a patient; and    visualizing localisation of the analogue in the body of the patient.    
     
     
         15 . The method of  claim 14  wherein the visualizing includes at least one of Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (MRI).  
     
     
         16 - 21 . (canceled)  
     
     
         22 . A method for preparing the analogue of  claim 1 , the method comprising: 
 providing                          wherein:    X is a leaving group selected from the group consisting of tosyl, mesityl, triflate and a halogen;    NH 2  and COOH are protected; 
 R is (C 1 -C 6 ) alkyl optionally substituted with thioether or ether oxygen atom; and  
   substituting a radioactive halogen for the leaving group of the precursor.    
     
     
         23 . The method of  claim 22  wherein the substitution comprises aliphatic nucleophilic substitution of tosyl, mesityl, or triflate with radioactive fluorine.  
     
     
         24 . The method of  claim 22  wherein the leaving group is a halogen, and the substitution comprises exchange of the leaving group with radioactive fluorine.