SEPTEMBER 1999 PRESS RELEASE
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Research paper p. 897 Research News & Views p. 849
A new chemistry between radioisotopes and antibodies
Every year, millions of people receive diagnostic and therapeutic treatments using radioisotopes linked to monoclonal antibodies to fight cancer and disease. One of these radioisotopes, technetium-99m, is commonly used for non-invasive imaging of organs or tumors. One of the problems with all of these approaches has been finding the right molecular "glue" to attach technetium-99m to antibodies without impairing the antibody's ability to specifically target the tumor cell of interest. In this issue, a team of European scientists report an ingenious chemical approach for hooking up tumor-specific antibodies to technetium-99m that can be accomplished as easily as mixing together two vials, making these radiopharmaceuticals within the reach of most trained hospital technicians.
Previous methods for attaching technetium-99m to antibody fragments (scFvs) were difficult and often required attachment of bulky chemical groups (chelators) that reduced the biological activity of the antibody. Andreas Plueckthun and his team have devised a new chemical synthesis that allows technetium (I) to form a complex with an aqua carbonyl group that can bind directly to histidine amino acids attached to the ends of scFvs. The chemical reaction represents a significant practical advance over previous methods, which required high pressures and temperatures, because it can be carried out in a technetium generator with carbon monoxide gas, at atmospheric pressure. When injected into mice, scFvs labeled by the new method showed no loss of binding activity and good stability. The scientists propose that the approach can also be extended to another radioisotope, rhenium, which is commonly used for therapy, and to labeling small molecules other than antibodies.
Contact (Author)
Andreas Plueckthun
Department of Chemistry
University of Zurich
CH-8507, Zurich Switzerland
Tel: 41 1 635 5570
Fax: 41 1 635 5712
e-mail [email protected]
Contact (Research news and views)
Alfred P. Sattelberger
Chemical Science & Technology Division
Los Alamos National Laboratory
Los Alamos, NM 87545
Tel: (505) 667-4457
Fax: (505) 665-4355
e-mail: [email protected]
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