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 degrees C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [In-111] 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 [In-111] In bimodal agent. Finally, the proof of concept of using it as a new tool for fluorescence-guided surgery has been shown.

Automated summary

A water-soluble fluorescent aza-BODIPY platform was prepared and bioconjugated onto a trastuzumab monoclonal antibody to specifically label HER-2-positive breast tumors. The resulting bioconjugate showed stability in serum and was radiolabeled for in vivo studies, demonstrating good tumor targeting. The developed multimodal imaging probe displayed good quantum yield of fluorescence and near infrared emission, showing potential for fluorescence-guided surgery.