Kit for radiolabelling with 68ga comprising a metal inhibitor

Abstract

The present invention relates to a kit for radiolabelling a targeting agent with gallium-68. The present invention also relates to the use of said kit for radiolabelling a targeting agent, a method for radiolabelling a targeting agent with gallium-68 using said kit, said kit and a method of preparation.

1 - 29 . (canceled) 
     
     
         30 . A kit for gallium-68 radiolabelling of a chelate-functionalized targeting agent for use in in-vivo PET imaging comprising:
 a suitable amount of acetate salt or buffer to balance at least an acidic pH eluate from a gallium-68 generator to a pH value between 3 to 5 when said generator is eluted in the kit;   a chelate-functionalized targeting agent, said chelate function being able to chelate gallium-68 in a radiolabelling reaction; and   a metal inhibitor, which is a co-chelating agent, capable of inactivating contaminating metals without interfering with the chelation between gallium-68 and said chelate-functionalized targeting agent, under the conditions of said radiolabelling reaction;
 wherein said radiolabelling reaction is carried out at a temperature near or equal to room temperature and at a pH of between 3 and 5, 
 wherein said chelate-functionalized targeting agent and said metal inhibitor are not chemically linked, 
 wherein said metal inhibitor is selected from the group consisting of DOTA, DTPA, a monosaccharide, a disaccharide and beta-cyclodextrin, 
 wherein said targeting agent of the chelate-functionalized targeting agent is selected from the group consisting of a peptide, a peptide comprising 2 to 20 amino acids, a polypeptide, an antibody, a nanobody, a diabody, an antibody fragment, a nucleic acid, an aptamer, an antisense oligonucleotide, and an organic molecule, and 
 wherein said chelate functional group of the chelate-functionalized targeting agent is selected from the group consisting of NOTA, NODAGA, Tris(hydroxypyridinone) (THP), HBED, DFO, 6SS, B6SS, PLED, YM103, and H 2 dedpa. 
   
     
     
         31 . The kit according to  claim 30 , wherein said acetate salt or buffer, chelate-functionalized targeting agent and metal inhibitor are lyophilized or co-lyophilized. 
     
     
         32 . The kit according to  claim 30 , wherein said chelate-functionalized targeting agent and metal inhibitor are lyophilized or co-lyophilized, and wherein said acetate salt or buffer is present separately and can be added subsequently. 
     
     
         33 . The kit according to  claim 30 , wherein the acetate salt or buffer comprises a quantity of acetate salt adjusted to the type of the gallium-68 generator used. 
     
     
         34 . The kit according to  claim 30 , wherein the acetate salt or buffer is present in a fixed concentration to balance the acidic pH eluate from a gallium-68 generator to a pH value between 3 to 5 when said generator is eluted in the kit after addition of HCl to the kit. 
     
     
         35 . The kit according to  claim 30 , wherein the acetate salt or buffer is present in an of amount between 5 mg and 1000 mg. 
     
     
         36 . The kit according to  claim 30 , wherein the metal inhibitor is present in a micromolar quantity. 
     
     
         37 . A process for preparing a radiolabelling kit according to  claim 30 , comprising the steps of:
 a) preparing or providing a solution comprising the suitable amount of acetate salt or buffer to balance at least the acidic pH eluate from a gallium-68 generator to a pH value between 3 to 5, preparing or providing the chelate-functionalized targeting agent and preparing or providing the metal inhibitor; and   b) lyophilizing the solution obtained in step a).   
     
     
         38 . A process for preparing a radiolabelling kit according to  claim 30 , comprising the steps of:
 a) preparing or providing a solution comprising the chelate-functionalized targeting agent and the metal inhibitor;   b) lyophilizing the solution obtained in step a), and   c1) adding the acetate salt as a powder in the obtained lyophilized product in step b), or   c2) adding an acetate buffer in the obtained lyophilized product in step b).   
     
     
         39 . A process for preparing a radiolabelling kit according to  claim 30 , comprising the steps of:
 a) preparing a solution comprising the acetate salt, the chelate-functionalized targeting agent and the metal inhibitor; and   b) optionally freeze the solution obtained in step a).   
     
     
         40 . The radiolabelling kit according to  claim 30 , wherein the monosaccharide is glucose, fructose or D-mannose. 
     
     
         41 . A method for radiolabelling a chelate-functionalized targeting agent with gallium-68 for use in in-vivo PET imaging, comprising the steps of:
 providing a kit according to  claim 30 , and   eluting a gallium-68 generator with an eluent comprising an acid in said kit, wherein the radiolabelling is performed at ambient or room temperature and at a pH between 3 and 5.   
     
     
         42 . The method according to  claim 41 , wherein the acid is HCl. 
     
     
         43 . An in vivo method for imaging a subject comprising the steps of:
 1) producing a gallium-68 radiolabelled chelate-functionalized targeting agent using the method of  claim 41 ;   2) administering said gallium-68 radiolabelled chelate-functionalized targeting agent to the subject; and   3) detecting said gallium-68 radiolabelled chelate-functionalized targeting agent in the subject using positron emission tomography (PET).