Covalent attachment of metal chelates to proteins:the stability in vivo and in vitro of the conjugate of albumin with a chelate of 111indium.

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Abstract
Human serum albumin was conjugated to 1-(p-benzenediazonium)-(ethylenedinitrilo)tetraacetic acid, a powerful chelating agent, and radioactive 111In ions were added specifically to the chelating groups. The product, with a specific radioactivity of about 1 mCi/mg of protein, was employed as a radiotracer in scintillation scanning studies with human volunteers. After injection (48 h), practically all of the label remains attached to albumin. This is confirmed by electrophoresis of serum proteins; 7 days after injection, 85% of the radioactivity in the serum is still in the albumin fraction. These observations agree with in vitro studies of the labeled albumin in human serum, where loss of the metal ion from the chelating group to the protein transferrin amounts to less than 3% after 1 wk and less than 5% after 2 wk. Measurements of the distribution of label in mice up to 23 days after injection suggest that metabolism of the labeled protein does not lead to binding of In ions by transferrin. The binding of In and other metal ions by transferrin previously posed a major impediment to the use of metal chelates for in vivo diagnostic procedures. Demonstration of the kinetic inertness of the chelate in these experiments suggests the use of related chelates as physical probes of biological systems.