The prime objective of this project is to develop an understanding of the fundamental chemistry of metal ions utilized in radioimmunotherapy, especially lead and bismuth. To accomplish this objective, we need to learn the coordination chemistry of the metal ions, in particular, their kinetic and thermodynamic behaviors in solution. This information can then be used to develop radiolabeled antibody systems for use in therapy. Substantive progress was made on two projects. First, Lead (II) complexes of the DOTA ligand were investigated in aqueous solution to model the behavior of the 212Pb alpha-particle emitter we wish to use for radioimmunotherapy of cancer. The kinetics of formation of the complex were measured and a possible mechanism for complex formation established. This information was employed to create an efficient method for labeling antibodies with 212 Pb. Secondly, the chemistry of bismuth (III) complexes with polyaminocarboxylate ligand DTPA and EDTA was investigated by physical methods including IR, NMR and X-ray diffraction. Both the CyclohexylDTPA complex which is stable in vivo and the parent DTPA complex show one carboxyl ligand that is less tightly bound than the others as evidenced in NMR spectra. The stability constant of the cyclohexyl derivative is, however, greater than that of the parent.
