Design Synthesis and Characterization of a Dual Modality Positron Emission Tomography Fluorescence Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging

摘要

A novel lysine-based trifunctional chelate >3 was designed, synthesized, and characterized, which bears both a chelating moiety (CHX-A”) for sequestering radiometals (⁸⁶Y or ¹¹¹In) and the near infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of >3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol-maleimide chemistry, thereby yielding immunoconjugate >2. Analysis of >2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate >2 binds to SKOV3 tumor cells comparably to native trastuzumab and thus may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging.