title: New bifunctional chelator for 64Cu-immuno-positron emission tomography.
abstract: A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron emission tomography imaging in animal models.
authors.forename: Darpan N
authors.initials: DN
authors.lastname: Pandya
authors.forename: Nikunj
authors.initials: N
authors.lastname: Bhatt
authors.forename: Ajit V
authors.initials: AV
authors.lastname: Dale
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hochun
authors.initials: H
authors.lastname: Lee
authors.forename: Yeong Su
authors.initials: YS
authors.lastname: Ha
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D003301:Copper Radioisotopes; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D017879:Isothiocyanates / Q000737:chemistry*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: C000593994:1,8-N,N'-bis-(carboxymethyl)-4-N''-(4'-isothiocyanatophenethyl)-1,4,8,11-tetraazacyclotetradecane; D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D017879:Isothiocyanates