Polymer precursors of radiolabeled compounds, and methods of making and using the same

Abstract

One aspect of the present invention relates to novel compounds that can be used to prepare radiolabeled compounds in an effective manner. A second aspect of the present invention relates to a method of synthesizing radiolabeled compounds.

1 . A polymer precursor compound represented by 1:  
       Poly-L-R—Y   1  
     wherein: 
 Poly represents a polymer;  
 L is selected from:  
                     
 R represents polycyclic aryl, or heteroaryl;  
 Y represents hydrogen, alkyl, alkoxyl, carbonyl, formyl, amido, amino, alkylamino, dialkylamino, carboxamido, acylamino, (heterocyclcyl)acylamino, alkylcarboxyamido, C(O)—R 4  or C(O)NH—R 4 ;  
 R 3  represents independently for each occurrence alkyl, alkenyl or alkynyl;  
 R 4  represents hydrogen, alkyl, alkenyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, peptide, protein, amino acid, antibody, nucleotide, nucleoside, or —(CH 2 ) m —R 80 ;  
 R 80  represents independently for each occurrence aryl, cycloalkyl, cycloalkenyl, heterocyclyl, or polycyclyl; and  
 m is an integer in the range 0 to 8 inclusive.  
 
   
   
       2 . The polymer precursor compound of  claim 1 , wherein L is R 3 —Sn—R 3 .  
   
   
       3 . The polymer precursor compound of  claim 2 , wherein Y is alkoxyl, formyl, amido, dialkylamino, carboxamido, alkoxyl, alkylcarboxyamido, C(O)—R 4  or C(O)NH—R 4 .  
   
   
       4 . The polymer precursor compound of  claim 3 , wherein Y is C(O)—R 4  or C(O)NH—R 4 .  
   
   
       5 . The polymer precursor compound of  claim 1  wherein R 4  is a peptide, protein, amino acid, antibody, nucleotide or nucleoside.  
   
   
       6 . The polymer precursor compound of  claim 4  wherein R 4  is a peptide, protein, amino acid, antibody, nucleotide or nucleoside.  
   
   
       7 . The polymer precursor compound of  claim 6  wherein R 4  is a peptide or protein.  
   
   
       8 . The polymer precursor compound of  claim 6  wherein R 4  is a nucleotide or a nucleoside.  
   
   
       9 . The polymer precursor compound of  claim 2  wherein R 3  is alkyl.  
   
   
       10 . The polymer precursor compound of  claim 2  wherein R 3  is butyl.  
   
   
       11 . The polymer precursor compound of  claim 11  wherein said polymer is functionalized by the moiety L on substantially all monomeric units.  
   
   
       12 . The polymer precursor compound of  claim 1  wherein said polymer is insoluble.  
   
   
       13 . The polymer precursor compound of  claim 12  wherein said polymer is polystyrene, polyurethrane, poly(ethylene-co-vinyl acetate), polyethylene, polystyrene/rubber, or poly(ethylene-co-propylene).  
   
   
       14 . The polymer precursor compound of  claim 13  wherein said polymer is polystyrene.  
   
   
       15 . A compound selected from the group consisting of: 
 Poly-(4S,5S)-2-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}phenyl)-3,4-dimethyl-5-1,3-oxazolidine)-co-divinylbenzene;    Poly-(4S,5S)-2-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}phenyl)-3,4-dimethyl-5-phenyl-1,3-oxazolidine)-co-divinylbenzene;    Poly-(3-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}benzaldehyde)-co-divinylbenzene;    Poly-(3-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}benzaldehyde)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}benzaldehyde)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}benzaldehyde)-co-divinylbenzene;    Poly-(3-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}benzoic acid)-co-divinylbenzene;    Poly-(3-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}benzoic acid)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}benzoic acid)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}benzoic acid)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}hippuric acid)-co-divinylbenzene,    (4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}hippuric acid)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}N,N-diethylethylenediamino benzamidyl)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}N,N-diethylethylenediamino benzamidyl)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}N-succinimidyl ester)-co-divinylbenzene;    Poly-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}N-succinimidyl ester)-co-divinylbenzene;    Poly-(4S,5S)-2-(5-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2,3-dihydrobenzofuran-7-yl)-3,4-dimethyl-5-phenyl-1,3-oxazolidine-co-divinylbenzene;    Poly-5-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2,3-dihydrobenzofuran-7-carbaldehyde-co-divinylbenzene; and    Poly-5-{Dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2,3-dihydrobenzofuran-7-carboxylic acid-co-divinylbenzene.    
   
   
       16 . A method for preparing a radiolabeled compound, the method comprising: reacting a compound of  claim 1  with an oxidant, a radiolabeled compound and optionally a buffer.  
   
   
       17 . A method of  claim 16 , further comprising a purification of the radiolabeled compound.  
   
   
       18 . A kit containing a radiolabeling system, comprising: a polymer precursor compound and instructions for using said polymer precursor compound, wherein said polymer precursor compound comprises the polymer precursor compound of  claim 1 .  
   
   
       19 . The kit of  claim 18  that further includes a filter or a filtration device.  
   
   
       20 . The kit of  claim 19  that further includes a chelating agent and optionally an auxiliary molecule.  
   
   
       21 . A method of synthesizing radiolabeled benzamides on a solid support comprising: 
 a) selecting a solid support comprising at least one compound attached to said solid support which compound comprises a benzoic acid moiety;    b) reacting said moiety of said compound attached to said solid support with at least one amine to afford a benzamide bound to a solid support; and    c) reacting said benzamide bound to said solid support with a radiolabeled compound or isotope, and an oxidant to yield said radiolabeled benzamides.    
   
   
       22 . The method of  claim 21  wherein the radioisotope is selected from the group consisting of  18 F,  11 C,  76 Br,  123 I,  131 I and  125 I.