Radiolabeled Silicon-Rhodamines as Bimodal PET/SPECT-NIR Imaging Agents

Abstract

Radiolabeled fluorescent dyes are decisive for bimodal imaging as well as highly in demand for nuclear- and optical imaging. Silicon-rhodamines (SiRs) show unique near-infrared (NIR) optical properties, large quantum yields and extinction coefficients as well as high photostability. Here, we describe the synthesis, characterization and radiolabeling of novel NIR absorbing and emitting fluorophores from the silicon-rhodamine family for use in optical imaging (OI) combined with positron emission tomography (PET) or single photon emission computed tomography (SPECT), respectively. The presented photostable SiRs were characterized using NMR-, UV-Vis-NIR-spectroscopy and mass spectrometry. Moreover, the radiolabeling conditions using fluorine-18 or iodine-123 were extensively explored. After optimization, the radiofluorinated NIR imaging agents were obtained with radiochemical conversions (RCC) up to 70% and isolated radiochemical yields (RCY) up to 54% at molar activities of g.t. 70 GBq/µmol. Radioiodination delivered RCCs over 92% and allowed to isolate the 123I-labeled product in RCY of 54% at a molar activity of g.t. 7.6 TBq/µmol. The radiofluorinated SiRs exhibit in vitro stabilities g.t. 70% after two hours in human serum. The first described radiolabeled SiRs are a promising step toward their further development as multimodal PET/SPECT-NIR imaging agents for planning and subsequent imaging-guided oncological surgery.

Dual-Labelling Strategies for Nuclear and Fluorescence Molecular Imaging: Current Status and Future Perspectives

“…More importantly, the radiofluorinated dye showed favourable pharmacokinetics and allowed for the simultaneous application of PET and optical imaging (OI) of the brain. More recently, the group Kopka et al studied radiolabelled silicon-rhodamines (SiRs) [68]. The yielded SiRs display distinctive near-infrared (NIR) optical properties, large quantum yields and high photo-stability.…”

“…Of particular importance in the design of BFCAs is the high complex stability and kinetic inertness as well as the use of appropriate functional groups for direct or linker-mediated conjugation with fluorescent dyes and/or biomolecules. In recent years, various BFCAs have been developed for SPECT/OI and PET/OI, using common SPECT ( 111 In, 99m Tc) and PET ( 64 Cu, 68 Ga, 89 Zr) radionuclides.…”

“…In SPECT, the gamma quanta are distributed statistically and in a rather disorderly way, whereas PET uses the defined collinear emission and detection of two 511 keV gamma photons, which are formed during the annihilation process of electrons and positrons (Figure 1). Commonly used gamma-emitting radionuclides for SPECT are 99m Tc, 111 In and 123 I, while for PET mostly the positron-emitting radionuclides 18 F, 64 Cu, 68 Ga, 89 Zr and 124 I are applied. For radiolabelling of longer circulating objects such as natural antibodies or nanomaterials, radionuclides with a rather longer half-life are used to follow the pharmacokinetic properties over several days.…”

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics

“…The combination of FI and NMI can overcome the obstacles of single modality imaging, allowing imaging with little radiation burden and unlimited penetration depth. For the construction of the bimodal probes in FI/NMI, however, the direct use of radiolabeled fluorescent dyes lack clear targeting sites ( Kanagasundaram et al, 2021 ; Peng et al, 2021 ). In this context, modified molecular probes and passively accumulated nanoparticles have been attributed to implement specific tumor uptake.…”

Efforts toward PET-Activatable Red-Shifted Silicon Rhodamines and Silicon Pyronine Dyes

“…= 648 nm, λ em. = 667 nm) with lower masses compared to other NIR BODIPY-derived dyes [ 14 ]. Other work proved that triazole-fused SiR is capable of chelating technetium-99m, resulting in a SPECT-activable NIR dye [ 99m Tc] 6 [ 15 ].…”