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

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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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