One-step (18)F-labeling of peptides for positron emission tomography imaging using the SiFA methodology.

Here we present a procedure to label peptides with the positron-emitting radioisotope fluorine-18 ((18)F) using the silicon-fluoride acceptor (SiFA) labeling methodology. Positron emission tomography (PET) has gained high importance in noninvasive imaging of various diseases over the past decades, and thus new specific imaging probes for PET imaging, especially those labeled with (18)F, because of the advantageous properties of this nuclide, are highly sought after. N-terminally SiFA-modified peptides can be labeled with (18)F(-) in one step at room temperature (20-25 °C) or below without forming side products, thereby producing satisfactory radiochemical yields of 46 ± 1.5% (n = 10). The degree of chemoselectivity of the (18)F-introduction, which is based on simple isotopic exchange, allows for a facile cartridge-based purification fully devoid of HPLC implementation, thereby yielding peptides with specific activities between 44.4 and 62.9 GBq µmol(-1) (1,200-1,700 Ci mmol(-1)) within 25 min.

[18F]azadibenzocyclooctyne ([18F]ADIBO): a biocompatible radioactive labeling synthon for peptides using catalyst free [3+2] cycloaddition.

N-Terminally azido-modified peptides were labeled with the novel prosthetic labeling synthon [(18)F]azadibenzocyclooctyne ([(18)F]ADIBO) using copper-free azide-alkyne [3+2]-dipolar cycloaddition in high radiochemical yields (RCYs). (18)F-Labeled [(18)F]ADIBO was prepared by nucleophilic substitution of the corresponding tosylate in 21% overall RCY (EOB) in a fully automated synthesis unit within 55 min. [(18)F]ADIBO was incubated with azide-containing peptides at room temperature in the absence of toxic metal catalysts and the formation of the triazole conjugate was confirmed. Finally, the azide-alkyne [3+2]-dipolar cycloaddition was shown to proceed with 95% radiochemical yield in ethanol within 30 min, allowing for a development of a kit-like peptide labeling approach with [(18)F]ADIBO.

Caging of carbonyl compounds as photolabile (2,5-dihydroxyphenyl)ethylene glycol acetals.

Aldehydes and ketones caged as 4-(2,5-dihydroxyphenyl)-1,3-dioxolanes are efficiently (Phi = 0.1-0.2) released in a good to excellent chemical yield upon irradiation with 300 nm light. Caged carbonyl compounds are prepared by their acetalization with (2,5-dimethoxyphenyl)ethylene glycol followed by oxidative demethylation to produce corresponding (1,3-dioxolane-4-yl)-1,4-benzoquinones. The latter acetals are photochemically inert but can be converted into photolabile hydroquinones by mild reduction in situ.