title: Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS.
abstract: The cross-bridged tetraamine ligand 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A) allows formation of a radio-copper complex with higher in vivo stability than that of the corresponding non-cross-bridged analog 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). The structure of the natCu(II) complex of CB-TE2A has been previously determined by X-ray crystallography; however, direct high-pressure liquid chromatography (HPLC) characterization of the corresponding 64Cu complex was inaccessible due to the inability to detect the complex by ultraviolet absorbance at the radiotracer level. A reverse-phase HPLC separation of a series of natCu(II)-tetraazamacrocyclic complexes, both traditional and cross-bridged, was developed and applied toward characterization and assessment of the purity of the corresponding no-carrier-added 64Cu-labeled complexes. Verification of the identity of copper-64-labeled compounds was also achieved by coupling this HPLC method with mass spectrometry. The radio-liquid chromatography/mass spectrometry methodology was further extended to study the in vivo metabolic fates of 64Cu-azamacrocyclic complexes.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Boswell
authors.forename: Paul
authors.initials: P
authors.lastname: McQuade
authors.forename: Gary R
authors.initials: GR
authors.lastname: Weisman
authors.forename: Edward H
authors.initials: EH
authors.lastname: Wong
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry; D003301:Copper Radioisotopes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D047028:Macrocyclic Compounds; D019275:Radiopharmaceuticals