Because they seek out and bind only to specific cells, monoclonal antibodies represent a powerful method for selectively carrying radionuclides to cancerous cells. Current techniques for attaching radionuclides to monoclonal antibodies rely on metal ion chelates. These often lack sufficient stability, and the radionuclide may be released by in vivo chemical processes or by the compounds that encapsulate the radioisotope inside a closed sphere of carbon. These new compounds possess extraordinary stability and should be completely inert to in vivo ion exchange processes. Recent experiments demonstrate that these complexes can easily withstand the nuclear decay energy produced by radioactive lanthanide metals used in nuclear medicine without releasing the radioactive decay products. Preliminary systemic toxicity studies show that they are relatively nontoxic in vivo. Phase I will focus on the synthesis, purification, and verification of these important properties. This will be accomplished by neutron activation of a model organometallic system containing a suitable isotope followed by complete characterization of the products produced by the neutron capture and subsequent decay processes. Phase II will focus on attaching the new compound to a monoclonal antibody and on characterizing the resulting conjugated complex.
It is expected that the Phase I research will demonstrate that these new organometallic compounds possess extraordinary resistance against release of the encapsulated radionuclide and will be superior to conventional chelates for conjugating radionuclides to monoclonal antibodies. Success in Phase II will result in a new type of radiolabel that can improve the performance of radioimmunoguided pharmaceuticals.