Toward preparation of antibody-based imaging probe libraries for dual-modality positron emission tomography and fluorescence imaging.

Two novel imaging agents trastuzumab-Cy5.5-CHX-A''1 and cetuximab-Cy7-CHX-A''2, bearing both a chelating moiety (CHX-A'') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, antibody-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e.g., A431), respectively, thereby demonstrating that the functionality of the targeting moiety is conserved. Hence, the described novel synthesis strategy can be applied to engineer other tumor-targeted monoclonal antibody based probes for multimodality imaging.