Mono-, di- or polysaccharide used as metal inhibitor in the preparation of 68ga-chelate-functionalized targeting agent

A method for radiolabelling a chelate-functionalized targeting agent for use in in-vivo PET imaging with a metal radionuclide, comprising the steps of:

• a) providing a chelate-functionalized targeting agent, able to chelate the metal radionuclide in a radiolabelling reaction, wherein the chelate functional group of the chelate-functionalized targeting agent is selected from the group consisting of DOTA, NOTA, NODAGA, HBED, DFO, EDTA, 6SS, B6SS, PLED, TAME, YM103 and H2dedpa;
• b) adding a metal inhibitor not chemically linked to said chelate-functionalized targeting agent, to the radiolabelling reaction obtained in a), said metal inhibitor being a co-chelating agent selected from the group consisting of:
• beta-cyclodextrin, a disaccharide and a monosaccharide, capable of inactivating metals other than metal radionuclides without interfering with the chelation between the metal radionuclide and the chelate-functionalized targeting agent, under the conditions of the radiolabelling reaction, thereby obtaining a mixture of the chelate-functionalized targeting agent of a) and the metal inhibitor of b) which are not chemically linked to each other when present in said mixture;
• and
• c) adding a metal radionuclide that is an isotope of a metal selected from the group consisting of copper, gallium, lutetium, indium, scandium, and zirconium to the mixture of a) and b) in an acetate buffer allowing to maintain the pH in the range 3-7;
• wherein the targeting agent of said 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.

A kit for radiolabelling of a chelate-functionalized targeting agent for use in in-vivo PET imaging comprising:

• a chelate-functionalized targeting agent, able to chelate a metal radionuclide in a radiolabelling reaction, wherein the chelate-functional group of the chelate-functionalized targeting agent is selected from the group consisting of DOTA, NOTA, NODAGA, HBED, DFO, EDTA, 6SS, B6SS, PLED, TAME, YM103 and H2dedpa;
• a metal inhibitor, which is not chemically linked to said chelate-functionalized targeting agent and which is a co-chelating agent selected from the group consisting of beta-cyclodextrin, a disaccharide and a monosaccharide, capable of inactivating metals other than metal radionuclides without interfering with the chelation between the metal radionuclide and the chelate-functionalized targeting agent, under the conditions of the radiolabelling reaction;
• a metal radionuclide that is an isotope of a metal selected from the group consisting of copper, gallium, lutetium, indium, scandium, and zirconium;
• and
• an acetate buffer, allowing to maintain the pH in the range 3-7,
• wherein the targeting agent of said 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.