title: Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb.
abstract: Radioisotopes of Pb(II) have been of some interest in radioimmunotherapy and radioimmunoimaging (RII). However, the absence of a kinetically stable bifunctional chelating agent for Pb(II) has hampered its use for these applications. 203Pb (T(1/2) = 52.02 h) has application potential in RII, with a gamma-emission that is ideal for single photon emission computerized tomography, whereas 212Pb (T(1/2) = 10 h) is a source of highly cytotoxic alpha-particles via its decay to its 212Bi (T(1/2) = 60 min) daughter. The synthesis of the novel bifunctional chelating agent 2-(4-isothiocyanotobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra- (2-carbamoyl methyl)-cyclododecane (4-NCS-Bz-TCMC) is reported herein. The Pb[TCMC]2+ complex was less labile to metal ion release than Pb[DOTA]2- at pH 3.5 and below in isotopic exchange experiments. In addition to increased stability to Pb2+ ion release at low pH, the bifunctional TCMC ligand was found to have many other advantages over the bifunctional 1,4,7,10-tetraazacyclodocane-1,4,7,10-tetraacetic acid (DOTA) ligand. These include a shorter and more straightforward synthetic route, a more efficient conjugation reaction to a monoclonal antibody (mAb), with a higher chelate to protein ratio, a higher percent immuroreactivity, and a more efficient radiolabeling reaction of the mAb-ligand conjugate with 203Pb.
authors.affiliation: Radioimmune and Inorganic Chemistry Section, ROB, DCS, Bethesda, Maryland 20892-1002, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Chappell
authors.forename: E
authors.initials: E
authors.lastname: Dadachova
authors.forename: D E
authors.initials: DE
authors.lastname: Milenic
authors.forename: K
authors.initials: K
authors.lastname: Garmestani
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006571:Heterocyclic Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017879:Isothiocyanates / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry; D007856:Lead Radioisotopes; D015394:Molecular Structure
chemical_list: C410212:2-(4-isothiocyanatobenzyl)-1,4,7,10--tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)cyclododecane; D002614:Chelating Agents; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D007856:Lead Radioisotopes