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

Nucl Med Biol. 1998 Jan;25(1):37-45. doi: 10.1016/s0969-8051(97)00154-6.

Abstract

We have investigated whether [186Re]-labeled chimeric monoclonal antibody 323/A3 (MAb c-323/A3) is as effective as [186Re]-labeled mouse 323/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xenografts OVCAR-3 and FMa. [186Re] 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 [186Re]-c-323/A3 and [186Re]-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 [186Re]-radioimmunotherapy in ovarian cancer patients.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Chelating Agents / chemistry
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Female
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Humans
  • Immunotoxins / chemistry
  • Immunotoxins / pharmacokinetics
  • Immunotoxins / therapeutic use*
  • Isoelectric Point
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / radiotherapy*
  • Ovarian Neoplasms / therapy*
  • Radioimmunotherapy*
  • Radioisotopes*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / therapeutic use*
  • Rhenium*
  • Tissue Distribution
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Chelating Agents
  • Immunotoxins
  • Radioisotopes
  • Recombinant Fusion Proteins
  • Rhenium
  • S-benzoylmercaptoacetyltriglycine
  • Glycine