""""""""The prime objective of this project is to develop a broad understanding of the fundamental chemistry of metal ions utilized in radioimmunotherapy, the foremost interest being Pb(II) and Bi(III). To accomplish this objective, an understanding of the coordination chemistry of metal ions, in particular, their kinetic and thermodynamic behaviors in solution, is required. Thus, Pb-212 potentially serves as an in vivo generator for delivery of the alpha-particle emitter Bi-212. Additionally, the alpha-particle emitter Bi-213, also being developed as a therapeutic agent, has decay characteristics that potentially obviate the requirement of a Hot Cell now required for Bi-212. To address the possible use of Pb-212, new chelating agents are required that are acid stable and capable of modulating or controlling the decay event of Pb-212 to Bi-212. Substantial progress has been made in obtaining Bi-213 from a prototype Ac-225 generator. Yields of greater than 10 mCi have been obtained for use in successfully radiolabeling monoclonal antibodies and studies initiated to solve radiolysis of ion-exchange support resins resulting in failure of the generator have yielded a new, reliable generator system for production of clinically useful Bi-213. This problem has been solved by use of a silica based ion-exchange Ac-225/Bi-213 generator that resists radiolytic failure with up to 25 mCi of Ac-225 on the resin. This generator system, now in its second modification, has been successfully tested and employed in pre-clinical studies with Bi-213 radiolabeled immunoproteins here at the NIH and elsewhere nationally. Therapeutic responses have been realized in several murine models and studies to optimize efficacy through fractionated dosing and appropriate scheduling of dosing are being planned. This project has also been discontinued and the various ongoing aspects absorbed where appropriate into projects Z01 SC 06353-16 RO """"""""""""""""Metal Chelate Conjugated Monoclonal Antibodies for Tumor Diagnosis and Therapy"""""""""""""""" and Z01 SC 06399-07 RO """"""""""""""""Thiol Containing Ligands for Pb(II) and Bi(III)"""""""""""""""".""""""""
