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Technical Report
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 antibody
Robert M Sharkey1, Thomas M Cardillo2, Edmund A Rossi3, Chien-Hsing Chang3, Habibe Karacay1, William J McBride2, Hans J Hansen2, Ivan D Horak2 & David M Goldenberg1
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 
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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