Synthesis and evaluation of a new bifunctional chelating agent for the preparation of radioimmunoconjugates.

The conjugation of radiometals to monoclonal antibodies results in agents for radioimmunoimaging and other medical applications. Due to remarkable ability to form stable metal complexes with a great number of metal ions in different oxidation states, polyaminocarboxylate chelates are useful tools for this purpose. Bifunctional chelators that can hold radiometals with high stability under physiological conditions are essential to avoid radiation damage to non-target organs. We have synthesized a new bifunctional chelate 2-(p-aminobenzyl)-1,3-propylenediamine-N,N,N',N'-tetraacetic acid by a simple method and studied the rate of loss of radioactivity from the radiolabeled (111In, 90Y) chelates to serum proteins in human serum at 37 degrees C. The relative stability constant of this new bifunctional chelate was found to be very similar to the underivated form. This chelate was conjugated to murine monoclonal antibody (B43) and immunoreactivity of the conjugated was determined by competitive binding analysis, which showed no significant change in its immunological activity. Biodistribution of the 111In radioconjugate was examined in conventional Balb/c and tumor-bearing (-OVCAR-3) athymic Balb/c mice.