Nitrogen-rich macrocyclic ligands, chelation complexes thereof, and process for selective chelation of radioactive bismuth ions with the ligands
Selective chelation of bismuth radionuclide ions from a mixture including actinium radionuclide ions involves exposing a ligand to an aqueous solution that includes bismuth radionuclide ions and actinium radionuclide ions under conditions whereby the bismuth radionuclide ions selectively chelate to the ligand for form cationic complexes of the bismuth radionuclide ions. and separating the cationic complexes of the bismuth radionuclide ions from the actinium radionuclide ions. The ligands have a structure based on a 12-membered cyclen ring and may include pendant functional groups that can be derivatized with biological targeting vectors for targeted alpha therapy.
1. A process, comprising:
forming an aqueous mixture comprising a ligand, bismuth radionuclide ions, and actinium radionuclide ions to form a cationic complex of the ligand and a bismuth radionuclide ion in the presence of the actinium radionuclide ions, the ligand having a structural formula
wherein A is selected from hydrogen and
E is selected from —NO 2 , —NH 2 , —SCN, —N 3 , -alkyne, maleimide, iodoacetamide, —NH(—C═S)NH—Z, triazole-Z, and thioether-Z; Z is a peptide, antibody, antibody fragment, peptide nucleic acid, nanoparticle, or other targeting moiety; and R is selected from
and
separating the cationic complex of the bismuth radionuclide ion from the actinium radionuclide ions.
2. The process of claim 1 , wherein the cationic complex has a structural formula
wherein:
M is a metal ion;
A is selected from hydrogen and
E is selected from —NO 2 , —NH 2 , —SCN, —N 3 , -alkyne, maleimide, iodoacetamide, —NH(—C═S)NH—Z, triazole-Z, and thioether-Z;
Z is a peptide, antibody, antibody fragment, peptide nucleic acid, nanoparticle, or other targeting moiety; and
R is selected from
3. A method, comprising:
forming an aqueous mixture comprising bismuth radionuclide ions, actinium radionuclide ions and a ligand having a formula
wherein A is selected from hydrogen and
E is selected from —NO 2 , —NH 2 , —SCN, —N 3 , -alkyne, maleimide, iodoacetamide, —NH(—C═S)NH—Z, triazole-Z, and thioether-Z, Z is a peptide, antibody, antibody fragment, peptide nucleic acid, or nanoparticle, and R is selected from
to form a cationic complex having a formula
and
separating the cationic complex from the actinium radionuclide ions.
4. The method according to claim 3 wherein:
the ligand has a formula
and
the cationic complex has a formula
5. The method according to claim 3 , wherein the ligand is selected from
6. The method according to claim 3 , wherein A is
7. The method according to claim 3 , wherein the aqueous mixture further comprises francium radionuclide ions, and separating the cationic complex from the actinium radionuclide ions further comprises separating the cationic complex from the francium radionuclide ions.