A functionalized heterobimetallic 99mTc/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 99mTc(CO3)+ core through the tridentate chelating iminodiacetic acid (IDA) clamp as a SPECT reporter. The heterodinuclear 99mTc/Re complex 8, as well as its non-radioactive dirhenium analog 7, was prepared in six steps. The 99mTc/Re agent is water-soluble and stable against histidine challenge. Its structural characterization was achieved by HPLC comparison with the non-radioactive complex 7. Upon excitation in the MLCT band at 321 nm, the compound 7 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 7 was >60% for all cell lines. Finally, cellular uptake studies of compound 7 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 99mTc/Re dinuclear compound 8 can be considered a potential pre- and intraoperative diagnostic probe.