Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody

Nat Med. 2005 Nov;11(11):1250-5. doi: 10.1038/nm1322. Epub 2005 Oct 30.

Abstract

Here we describe molecular imaging of cancer using signal amplification of a radiotracer in situ by pretargeting a multivalent, bispecific antibody to carcinoembryonic antigen (CEA), which subsequently also captures a radioactive hapten-peptide. Human colon cancer xenografts as small as approximately 0.15 g were disclosed in nude mice within 1 h of giving the radiotracer, with tumor/blood ratios increased by >or=40-fold (approximately 10:1 at 1 h, approximately 100:1 at 24 h), compared to a (99m)Tc-labeled CEA-specific F(ab') used clinically for colorectal cancer detection, while also increasing tumor uptake tenfold ( approximately 20% injected dose/g) under optimal conditions. This technology could be adapted to other antibodies and imaging modalities.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / administration & dosage
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use*
  • Carcinoembryonic Antigen / immunology
  • Carcinoembryonic Antigen / metabolism
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / radiotherapy*
  • Female
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Mice
  • Mice, Nude
  • Models, Biological
  • Neoplasm Transplantation
  • Radioimmunotherapy*
  • Radionuclide Imaging*
  • Technetium / pharmacokinetics
  • Time Factors
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Antibodies, Bispecific
  • Carcinoembryonic Antigen
  • Iodine Radioisotopes
  • Technetium