Aminoferrocene-Based Anticancer Prodrugs Labelled with Cyanine Dyes for in vivo Imaging

N-alkylaminoferrocene-based (NAAF) prodrugs are activated in the presence of reactive oxygen species (ROS), based on which these prodrugs target cancer cells (high ROS) and do not affect normal cells (low ROS). To gain some insights into their mode of action in vivo, we have investigated the biodistribution of F-18-labelled NAAF prodrugs in tumor-bearing mice by positron emission tomography (PET). Due to the short half-life of F-18, the experimental time frame was restricted to 60 min. To extend the observation window, a more stable marker is required. In this paper, we report on conjugates of NAAF prodrugs with two cyanine dyes Cy5 and Cy7 including details of their synthesis, characterization and basic properties in cell free settings and their cellular uptake in representative human cancer cells. Finally, the Cy5 conjugate was subjected to in vivo fluorescence imaging studies to determine the prodrug biodistribution over 24 h.

Automated summary

NAAF prodrugs are activated in the presence of ROS to target cancer cells, PET imaging is used to investigate their biodistribution in vivo, and a stable marker is needed to extend the observation window.