[186Re]-labeled mouse and chimeric monoclonal antibody 323/A3: A comparison of the efficacy in experimental human ovarian cancer

Abstract We have investigated whether [ 186 Re]-labeled chimeric monoclonal antibody 323/A3 (MAb C-323/A3) is as effective as [ 186 Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [ 186 Re] was conjugated to MAbs with the use of the chelate S -benzoylmercaptoacetyltriglycine ( S -benzoyl-MAG3). The maximum number of metal-MAG3 groups that could be conjugated to one MAb molecule accepting a minimal initial increase of the blood clearance (15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With these molar ratios the immunoreactivity of both MAbs was maintained. An inverse relationship was observed between the protein dose of c-323/A3 and its blood clearance. Both [ 186 Re]-c-323/A3 and [ 186 Re]-m-323/A3 were comparable in the inhibition of the tumor growth when higher protein doses were used. Together with the expected lower immunogenicity, our results imply that c-323/A3 is preferable for use in [ 186 Re]-radioimmunotherapy in ovarian cancer patients.