Rhenium and technetium-complexed silicon rhodamines as near-infrared imaging probes for bimodal SPECT- and optical imaging

Radiolabelled fluorescent dyes are decisive for bimodal imaging and currently in demand for scintigraphic and optical imaging. This powerful method allows the combination of nuclear imaging (e.g. SPECT-imaging) and optical imaging which leads to synergistic effects, resulting in high spatial resolution and high tissue penetration from the whole body to the subcellular level. The new approaches in tumor imaging and its resection enables the accurate differentiation of healthy and diseased (e.g. tumor) tissues. Organic dyes belonging to the rhodamine family show unique optical properties such as high quantum yields, large extinction coefficients, absorption and emission properties in the optical window. The goal of this work was the development of small molecule near-infrared (NIR) light-emitting silicon-rhodamines (SiR) for scintigraphic and optical imaging. We utilized the dyes for copper(I)-catalyzed alkyne-azide [3+2]-cycloaddition to receive respective 1,2,3-triazoles for complexing the prominent SPECT-radiometal 99mTc(I)- and rheniumtricarbonyl core using the click-to-chelate concept from Mindt et al. The dyes were fully characterized using NMR-, UV/VIS/NIR-spectroscopy, IR and mass spectrometry. The presented silicon rhodamines with optical properties in the near-infrared region with emission wavelengths of ca. 650 nm and quantum yields in aqueous solution of up to 0.10 were received in seven reaction steps. The determined extinction coefficients of ca. 150.000 M-1cm-1 show promising results, making them potentially useful for bimodal imaging. Furthermore the dyes were prepared as precursors for radiolabelling with the SPECT-compatible radiometal technetium-99m. Corresponding rhenium-Si-rhodamines [used as a non-radioactive technetium-surrogate] were chemically characterized as well. Subsequently perfomed radiolabelling experiments have shown radiochemical yields of up to 59% and a radiochemical purity greater than 98%. The complexes show high stability both in aqueous solution and even in challenging experiments with histidine under physiological conditions. The first-in-class dyes have been synthesized to elucidate their potential for fluorescence- and radio-guided surgery. The non-targeted radiolabelled rhodamine dyes are subject of ongoing biological evaluations and the incorporation of biovectors into the dye for selective (tumor) targeting are topics of current research.