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Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody
Authors:Sharkey Robert M  Cardillo Thomas M  Rossi Edmund A  Chang Chien-Hsing  Karacay Habibe  McBride William J  Hansen Hans J  Horak Ivan D  Goldenberg David M
Affiliation:Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, New Jersey 07109, USA.
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.
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