New anti-Cu-TETA and anti-Y-DOTA monoclonal antibodies for potential use in the pre-targeted delivery of radiopharmaceuticals to tumor

Hybridoma. 1998 Apr;17(2):125-32. doi: 10.1089/hyb.1998.17.125.

Abstract

Monoclonal antibodies were raised against yttrium(III)-1, 4, 7, 10-tetraazacyclododecane-N,N',N''N'''--tetraacetic acid (Y-DOTA) and copper(II)-1, 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 x 10(8) M(-1)) was further characterized by competitive ELISA. Gd-DOTA competed as well as Y-DOTA, whereas In-DOTA required 740x 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibody Affinity
  • Haptens / chemistry
  • Haptens / immunology
  • Heterocyclic Compounds / immunology*
  • Hybridomas / immunology
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / immunology*
  • Radioimmunotherapy / methods*
  • Radiopharmaceuticals / administration & dosage*
  • Sensitivity and Specificity

Substances

  • Antibodies, Monoclonal
  • Haptens
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Radiopharmaceuticals
  • copper(II)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid
  • yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid