A functionalized heterobimetallic99mTc/Re complex as a potential dual-modality imaging probe: synthesis, photophysical properties, cytotoxicity and cellular imaging investigations

Abstract

A novel bimodal fluorescent/radiolabelled probe based on a pyridyltriazole scaffold (known as pyta) is reported here. The final dual imaging agent combines carboxylate functionalization, for biomolecule conjugation, with two distinct metal chelating sites: a pyta-based tricarbonylrhenium moiety as a fluorescent probe and a (99m)Tc(CO3)(+) core through the tridentate chelating iminodiacetic acid (IDA) clamp as a SPECT reporter. The heterodinuclear (99m)Tc/Re complex , as well as its non-radioactive dirhenium analog , was prepared in six steps. The (99m)Tc/Re agent is water-soluble and stable against histidine challenge. Its structural characterization was achieved by HPLC comparison with the non-radioactive complex . Upon excitation in the MLCT band at 321 nm, the compound exhibits a bright green luminescence centered at 496 nm, with a quantum yield of 0.86% in Tris buffer, pH 7.4. Additionally, the influence of this compound on cell viability was tested on malignant cell lines (A549, HT29 and MCF-7 human lung, colon and breast carcinomas, respectively). Cell viability after 72 h incubation at 37 °C with 300 μmol of complex was >60% for all cell lines. Finally, cellular uptake studies of compound were performed by fluorescent microscopy, showing that the complex was clearly detected at the cellular level in A549 cells and to a lesser extent in HT29 cells. Taking into consideration the luminescent properties, the good radiochemical purity and the promising biological data (in vitro stability, non-toxicity, and cell tracking in two cell lines), the functionalized (99m)Tc/Re dinuclear compound can be considered a potential pre- and intraoperative diagnostic probe.