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.

Today, there is a very strong demand for versatile near-infrared imaging (NIR) agents suitable for non-invasive optical imaging in living organisms (in vivo imaging). We created here a family of NIR emitting macromolecules that take advantage of the unique structure of dendrimers. In contrast to existing fluorescent dendrimers bearing fluorophores at their periphery or in their cavities, a NIR fluorescent structure is incorporated in the core of the dendrimer. By using the poly(amidoamine) dendrimer structure, we want to promote the biocompatibility of the NIR-emissive system and to have functional groups available at the periphery to obtain specific biological functionalities such as the ability to deliver drugs or for targeting biological location. We report here the divergent synthesis and characterization by NMR and mass spectrometries of poly(amidoamine) dendrimers derived from the fluorescent NIR-emitting anthraquinone core (AQ-PAMAF). AQ-PAMAFs ranging from the generation -0.5 up to 3 were synthesized with a good level of control resulting in homogeneous and complete dendrimers. Absorption, excitation and emission spectra as well as quantum yields of AQ-PAMAF have been determined in aqueous solutions and compared with the corresponding properties of the AQ-core. It has been demonstrated that absorption bands of AQ-PAMAF range from UV to 750 nm while the emission is observed in the range of 650 to 950 nm. Fluorescence macroscopy experiments confirmed that the NIR signal of AQ-PAMAF can be detected with a satisfactory signal-to-noise ratio in aqueous solution, in blood and through 1 mm thick tissue-mimicking phantom. Results show that our approach is highly promising for the creation of an unprecedented generation of versatile NIR-emitting agents.

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...

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