Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb

Nucl Med Biol. 2000 Jan;27(1):93-100. doi: 10.1016/s0969-8051(99)00086-4.

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.

MeSH terms

  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Heterocyclic Compounds / blood
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Isothiocyanates / blood
  • Isothiocyanates / chemical synthesis*
  • Isothiocyanates / chemistry
  • Lead Radioisotopes*
  • Molecular Structure

Substances

  • 2-(4-isothiocyanatobenzyl)-1,4,7,10--tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)cyclododecane
  • Chelating Agents
  • Heterocyclic Compounds
  • Isothiocyanates
  • Lead Radioisotopes