Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

A water-soluble
fluorescent aza-BODIPY platform (Wazaby) was prepared
and functionalized by a polyazamacrocycle agent and a bioconjugable
arm. The resulting fluorescent derivative was characterized and bioconjugated
onto a trastuzumab monoclonal antibody as a vector. After bioconjugation,
the imaging agent appeared to be stable in serum (>72 h at 37 °C)
and specifically labeled HER-2-positive breast tumors slices. The
bioconjugate was radiolabeled with [111In] indium and studied in vivo. The developed monomolecular multimodal imaging
probe (MOMIP) is water-soluble and chemically and photochemically
stable, emits in the near infrared (NIR) region (734 nm in aqueous
media), and displays a good quantum yield of fluorescence (around
15%). Single-photon emission-computed tomography and fluorescence
imaging have been performed in nude mice bearing HER2-overexpressing
HCC1954 human breast cancer xenografts and have evidenced the good
tumor targeting of the [111In] In bimodal agent. Finally,
the proof of concept of using it as a new tool for fluorescence-guided
surgery has been shown.