title: Conjugation of DOTA-like chelating agents to peptides and radiolabeling with trivalent metallic isotopes.
abstract: Peptides can be labeled with various trivalent radiometals for imaging or targeted radionuclide-therapy applications. The peptide is first conjugated to a chelating agent that is able to form stable complexes with the radionuclide of interest. This conjugation step can be carried out as part of the solid-phase peptide synthesis, or it can be undertaken in the solution phase after synthesis and purification of the peptide. The latter route, described here, involves reacting a molar excess of the activated tri-tert-butyl ester-derivatized chelator with a designated free amino group of a peptide analog, in which all other reactive amines are protected, in the presence of a coupling agent. The conjugate molecule is then purified prior to deprotection and further purification by HPLC. The product can be radiolabeled by addition of a suitable metal salt, followed, if necessary, by removal of the unchelated metal. The entire process of conjugation, purification and radiolabeling should take approximately 12.5 h.
authors.affiliation: Nuclear Medicine Research Laboratory, St. Bartholomew's Hospital, London, EC1A 7BE, UK. jane.sosabowski@cancer.org.uk
authors.forename: Jane K
authors.initials: JK
authors.lastname: Sosabowski
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mather
mesh_terms: D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D007205:Indium Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008187:Lutetium / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D015021:Yttrium Radioisotopes / Q000737:chemistry*
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D008670:Metals; D010455:Peptides; D015021:Yttrium Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium