Antibodies labeled with metallic radionuclides: influence of nuclide chemistry on dose distribution

An antibody with human CEA specificity has been labeled with either yttrium-90, scandium-47, or indium-111, via a diethylenetriamine pentaacetic acid (DTPA) link covalently bound to the protein. The clearance of these proteins from the blood of mice can be described by a single exponential; the half-life decreases in the order indium-111 greater than yttrium-90 greater than scandium-47. Associated with the blood clearance is an uptake of radioactivity into the liver; scandium-47 has the highest concentration, indium-111 has the least, and yttrium-90 is intermediate. There is no correlation between these results and the equilibrium stability constants of the metals with DTPA-like ligands. The results obtained show that, in vivo, scandium-47 and yttrium-90 are more easily displaced from DTPA by other ions than is indium-111. They also show that free DTPA is able to extract yttrium-90 and scandium-47, but not indium-111, from the liver of treated animals, indicating that indium-111 is resistant to ligand exchange reactions in vivo. These data indicate that 1) the equilibrium stability constant is not a good indicator of the in vivo stability of metal-labeled proteins and 2) it is possible to manipulate the ion distribution and therefore the dose from scandium-47 and yttrium-90 after injection of the labeled proteins.