Convenient PET-tracer production via SuFEx 18F-fluorination of nanomolar precursor amounts.

Recently, a protocol for radiolabeling of aryl fluorosulfates ("SuFEx click radiolabeling") using ultrafast 18F/19F isotopic exchange has been reported. Although promising, the original procedure turned out to be rather inefficient. However, systematic optimization of the reaction parameters allowed for development of a robust method for SuFEx radiolabeling which obviates the need for azeotropic drying, base addition and HPLC purification. The developed protocol enabled efficient 18F-fluorination of low nanomolar amounts of aryl fluorosulfates in highly diluted solution (micromolar concentrations). It was successfully used to prepare a series of 29 18F-fluorosulfurylated phenols - including modified ezetimibe, α-tocopherol and etoposide, the two tyrosine derivatives Boc-Tyr([18F]FS)-OMe and H-Tyr([18F]FS)-OMe, the FAP-specific ligand [18F]FS-UAMC1110, and the DPA-714 analog [18F]FS-DPA - in fair to excellent yields. Preliminary evaluation demonstrated sufficient in vivo stability of radiofluorinated electron rich or neutral {Boc-Tyr([18F]FS)-OMe), H-Tyr([18F]FS)-OMe and [18F]FS-DPA} aryl fluorosulfates. Furthermore, [18F]FS-DPA was identified as a promising tracer for visualization of TSPO expression.

18F-Labeled magnetic nanovectors for bimodal cellular imaging.

Surface modification of nanocarriers enables selective attachment to specific molecular targets within a complex biological environment. Besides the enhanced uptake due to specific interactions, the surface ligands can be utilized for radiolabeling applications for bimodal imaging ensured by positron emission topography (PET) and magnetic resonance imaging (MRI) functions in one source. Herein, we describe the surface functionalization of magnetite (Fe3O4) with folic acid as a target vector. Additionally, the magnetic nanocarriers were conjugated with appropriate ligands for subsequent copper-catalyzed azide-alkyne cycloaddition or carbodiimide coupling reactions to successfully achieve radiolabeling with the PET-emitter 18F. The phase composition (XRD) and size analysis (TEM) confirmed the formation of Fe3O4 nanoparticles (6.82 nm ± 0.52 nm). The quantification of various surface functionalities was performed by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet-visible microscopy (UV-Vis). An innovative magnetic-HPLC method was developed in this work for the determination of the radiochemical yield of the 18F-labeled NPs. The as-prepared Fe3O4 particles demonstrated high radiochemical yields and showed high cellular uptake in a folate receptor overexpressing MCF-7 cell line, validating bimodal imaging chemical design and a magnetic HPLC system. This novel approach, combining folic acid-capped Fe3O4 nanocarriers as a targeting vector with 18F labeling, is promising to apply this probe for bimodal PET/MR-studies.

Reversible Covalent Assembly of Nanoparticles through On-Surface Diels-Alder Reaction.

We demonstrate here a controlled assembly of individual nanoscale building blocks into defined architectures based on chemospecific covalent bonding interactions. For this purpose, α-Fe2O3, γ-Fe2O3, and SiO2 nanoparticles decorated with surface-conjugated organic ligands were used for performing on-surface Diels-Alder reactions. Driven through their chemical affinity and surface-grafted complementary functionalities, nanoparticles underwent click-reactions to produce covalently organized nanostructures. An advantage of using the Diels-Alder reaction is its reversible nature, which was used to click and unclick the nanoparticles on demand. The efficiency and chemical specificity of this approach opens up another synthetic access to unify materials with complementary properties, where the thermoresponsive nature of particle assemblies imparts to them a fully reversible character. The covalent conjugation strategies demonstrated in this work potentially allow the use of a diverse range of particles and ligands for their applications in different disciplines such as medicine, optics, or photonics. The nanoparticles morphology and crystalline nature were investigated by TEM and XRD analysis, while the presence of surface attached groups was verified by NMR, FTIR, UV-vis, and ζ potential measurements.