Nature Medicine 11, 1250 - 1255 (2005)
Published online: 30 October 2005; | doi:10.1038/nm1322
Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibodyRobert M Sharkey1, Thomas M Cardillo2, Edmund A Rossi3, Chien-Hsing Chang3, Habibe Karacay1, William J McBride2, Hans J Hansen2, Ivan D Horak2
& David M Goldenberg11
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, New Jersey 07109, USA. 2
Immunomedics, Inc., 300 American Road, Morris Plains, New Jersey 07950, USA. 3
IBC Pharmaceuticals, Inc., 300 American Road, Morris Plains, New Jersey 07950, USA.
Correspondence should be addressed to David M Goldenberg dmg.gscancer@att.net 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  0.15 g were disclosed in nude mice within 1 h of giving the radiotracer, with tumor/blood ratios increased by  40-fold (10:1 at 1 h, 100:1 at 24 h), compared to a 99mTc-labeled CEA-specific F(ab') used clinically for colorectal cancer detection, while also increasing tumor uptake tenfold (20% injected dose/g) under optimal conditions. This technology could be adapted to other antibodies and imaging modalities.
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