Molecular imaging is a fundamental tool to improve the patient’s outcome in the theranostics of many non-communicable diseases (NCDs) hence the development of targeted probes able to identify the disease early and reliably is a pressing need. A closely related area focus on the monitoring of oxygen levels in tissue in NCDs as reduced oxygen levels are directly related to poor prognosis of many diseases. New directions in molecular imaging are stressing the importance of targeted multimodal probes, active on more than one imaging technique. An increasing interest is focusing on positron emission tomography (PET) due to the available variety of radioisotopes such as gallium-68 that can be generator-produced and readily available in preclinical/clinical setups. Optical imaging is also receiving increasing attention, especially in the near-infrared (NIR) window due to the reduced absorption of tissue, as NIR dyes allow imaging in vitro and/or in vivo (superficial structures or internal structures through intraoperative or endoscopy illumination). We report hereby the synthesis of targeted heptamethine cyanine dyes with improved solubility in physiological media and different substituents that allow for the application of the dye core as a multifunctional structure. The NIR dyes incorporate specific peptides (e.g. bombesin) targeting widely known receptors overexpressed in cancer as homing moieties but the bioactive molecule could be exchanged by varying the substrates in the developed linking strategies. We studied the incorporation of different metals of interest in nuclear imaging techniques and characterized the obtained “cold” compounds. Furthermore, the presence of a redox-active moiety allow for the potential application of the aforementioned dyes as molecular oxygen sensors. The dyes were studied in vitro in living PC-3 prostate cancer cells by single photon confocal microscopy and super-resolution confocal microscopy in order to evaluate their uptake behavior and localization within the cell.

Synthesis of targeted heptamethine cyanine dyes as potential PET/NIR multimodal imaging agents and evaluation of their role as oxygen sensors

256th National Meeting (2018)

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