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  • Title: Optimization of labeling and metabolite analysis of copper-64-labeled azamacrocyclic chelators by radio-LC-MS.
    Author: Boswell CA, McQuade P, Weisman GR, Wong EH, Anderson CJ.
    Journal: Nucl Med Biol; 2005 Jan; 32(1):29-38. PubMed ID: 15691659.
    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.
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