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The design and synthesis of 18F-radiolabelled and fluorescent dual imaging agents allowing bimodal PET/FLI imaging is a current challenge. We report herein the development of a cyanine-based [18F]F-C-glycosyl dual imaging probe for fluorescence imaging (FLI) and a robust [18F]F–C bond for positron emission tomography (PET) imaging. Interestingly, the proposed strategy allows a late-stage coupling of the probe with various vectors, successfully illustrated by conjugation to c(RGDfK) via CuAAC for αvβ3 integrin targeting. As attested by the in vitro evaluation, the novel dual agent demonstrates affinity for αvβ3 integrins in the nanomolar range (IC50 = 398 nM). This fluorescent dual agent was fully characterized by photophysical measurements (λabs/λem = 643/660 nm, Φfluo = 0.13) and by NMR spectroscopy, revealing some significant chemical shift modifications of the cyanine polymethine chain depending on the counter anion. A mesylated derivative of the cyanine-containing probe allowed the successful direct 18F-radiolabelling with a radiochemical yield of 18%. The 18F-radiolabelled fluorescent probe, obtained via [18F]F–C bond formation, allows subsequent vector introduction for in vivo targeting, opening a broad scope of applications in imaging modalities and therapy. [ABSTRACT FROM AUTHOR]

Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable C-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [18F]F-C bond formation. The non-radioactive dual imaging probe coupled with two c(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on αvβ3 integrin (IC50 = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery. [ABSTRACT FROM AUTHOR]

This work describes the development of new 6-[18F]fluoro-carbohydrate-based prosthetic groups equipped with an azido arm that are able to participate in copper(I)-catalyzed cycloadditions for 18F labeling of biomolecules under mild conditions. The radiolabeling in high radiochemical yields (up to 68 ± 6%) of these different prosthetic groups is presented. The flexibility of the azido arm introduced on the carbohydrate moieties allows efficient click reactions with different alkyne functionalized peptides such as gluthation or Arg-Gly-Asp derivatives in order to prepare glycopeptides. The radiosyntheses of 18F-labeled glycopeptides proceed in high radiochemical yields (up to 76%) in an automated process with excellent radiochemical purity. The addition of a sugar moiety on peptides should enhance the bioavailability, pharmacokinetic, and in vivo clearance properties of these glycopeptides, compared with the unlabeled native peptide, and these properties are highly favorable for positron emission tomography imaging. A high uptake of 18F- β-gluco-c(RGDfC) is shown by positron emission tomography imaging in a subcutaneous abscess model in the rat, revealing the potential of this tracer to monitor integrin expression as a part of inflammation and/or angiogenesis processes. [ABSTRACT FROM AUTHOR]

The design of bifunctional chelating agents (BFCA) allowing straightforward radiometal labelling of biomolecules is a current challenge. We report herein the development of a bifunctional chelating agent based on a DOTA chelator linked to a C -glycosyl compound, taking advantage of the robustness and hydrophilicity of this type of carbohydrate derivative. This new BFCA was coupled with success by CuAAC with c(RGDfK) for α v β 3 integrin targeting. As attested by in vitro evaluation, the conjugate DOTA- C -glyco-c(RGDfC) demonstrated high affinity for α v β 3 integrins (IC 50 of 42 nM). [ 68 Ga]Ga-DOTA- C -glyco-c(RGDfK) was radiosynthesized straightforwardly and showed high hydrophilic property (log  D 7.4 = -3.71) and in vitro stability (>120 min). Preliminary in vivo PET study of U87MG engrafted mice gave evidence of an interesting tumor-to-non-target area ratio. All these data indicate that [ 68 Ga]Ga-DOTA- C -glyco-c(RGDfK) allows monitoring of α v β 3 expression and could thus be used for cancer diagnosis. The DOTA- C -glycoside BFCA reported here could also be used with various ligands and chelating other (radio)metals opening a broad scope of applications in imaging modalities and therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)