A clickable C-glycosyl scaffold for RGD peptide dimer labelling and application in bimodal [18F]PET/NIRF imaging
Abstract
Objective
A trend in molecular imaging is to combined two modalities, advantages of one compensate limitations of the second. Combining PET (Positron Emission Tomography) and NIRF (Near Infra-Red Fluorescence) imaging conjugates the non-invasive diagnosis of PET with the intraoperative imaging guided surgery or ex vivo histopathology of NIRF imaging.2,3 We developed a dual [18F]PET/NIRF imaging agent based on a single probe detectable with both modalities, which is the best way to facilitate the use of bimodal imaging.
Methods
18F is a suitable isotope to form stable C-F bond and provide radiotracers with molar activity.3 A cyanine which is one of the most used fluorophores for biomedical applications was selected as the fluorescent dye. A C-glycosyl scaffold is functionalized in a regiocontrolled manner in order to introduce the fluorescent derivative (Cy-5) and the fluorine bound to a carbon, optimal for in vivo stability. Two c(RGDfK) peptides targeting integrins, overexpressed in some malignant tumours, were introduced by CuAAC.
Results and Conclusion
The binding affinities towards integrins are higher than c(RGDfK) peptide reference, highlighting the benefit of the divalence (IC50 10-16 nM vs 40 nM for the reference c(RGDfK). The in vitro optical imaging of the synthetic dual agents evaluated in U87MG cells shows a great cellular incorporation. The 18F-radiofluoration was successfully performed on the radiolabeling precursor displaying the cyanine moiety. The radiosynthesis automation in an AllInOne (AIO) synthesizer and the in vivo PET and NIRF imaging are in development. According to in vitro data and promising radiofluoration, this dual tool could be a valuable agent in bimodal imaging for diagnosis and guided surgery.