New Anti-Cu-TETA and Anti-Y-DOTA Monoclonal Antibodies for Potential Use in the Pre-Targeted Delivery of Radiopharmaceuticals to Tumor

Abstract

Monoclonal antibodies were raised against yttrium(III)-l, 4, 7, 10-tetraazacyclododecane-N,N′,N″,N‴— tetraacetic acid (Y-DOTA) and copper(II)-l, 4, 8, 11-tetraazacyclotetradecane-N,N′,N″,N‴-tetraacetic acid (Cu-TETA). Four hybridomas with high Y-DOTA binding activity and one hybridoma with Cu-TETA activity were selected. MAbs were purified from mouse ascites by Protein A affinity chromatography and characterized. Affinity constants were determined by equilibrium dialysis and the highest affinity Y-DOTA MAb (K_aff = 1.9 × 10⁸ M^-1) was further characterized by competitive ELISA. Gd-DOTA competed as well as Y-DOTA, whereas In-DOTA required 740× higher concentrations for 50% inhibition of this Y-DOTA MAb binding to human serum albumin-Y-DOTA-coated microtiter plates. These anti-metal chelate MAbs have potential use as vehicles for the pretargeted delivery of radiometal chelates to tumors.