Abstract
Currently, only a few 18F-radiolabeling methods were conducted in aqueous media, with non-macroelement fluoride acceptors and stringent conditions required. Herein, we describe a one-step non-solvent-biased, room-temperature-driven 18F-radiolabeling methodology based on organophosphine fluoride acceptors. The high water tolerance for this isotope-exchange-based 18F-labeling method is attributed to the kinetic and thermodynamic preference of F/F over the OH/F substitution based on computational calculations and experimental validation. Compact [18/19F]di-tert-butyl-organofluorophosphine and its derivatives used as 18F-labeling synthons exhibit excellent stability in vivo. The synthons are further conjugated to several biomolecular ligands such as c(RGDyk) and human serum albumin. The one-step labeled biomolecular tracers demonstrate intrinsic target imaging ability and negligible defluorination in vivo. The current method thus offers a facile and efficient 18F-radiolabeling pathway, enabling further widespread application of 18F.
Highlights
Only a few 18F-radiolabeling methods were conducted in aqueous media, with nonmacroelement fluoride acceptors and stringent conditions required
To synthesize 18F-labeled Positron emission tomography (PET) tracers, traditional labeling methods are mostly based on carbon-fluorine bond formation, which usually demands multiple steps and/or harsh reaction conditions such as heating at high temperatures in organic media[3]
Results of radiochemical yields (RCYs) are presented by means ± standard deviations (n = 3) aP-F bond energy calculated by Gaussian 09 bAll RCYs are experimental values acquired under the same conditions, where 1.0 μmol of precursor was dissolved in 100 μL of dimethyl sulfoxide (DMSO), 100 μL of [18F]F- aqueous solution from the cyclotron target was added, and the reaction was carried out at 75 °C for 15 min
Summary
Only a few 18F-radiolabeling methods were conducted in aqueous media, with nonmacroelement fluoride acceptors and stringent conditions required. Several direct aqueous 18F-labeling approaches have been reported, using organofluorosilicons[2, 9,10,11,12,13,14,15], aluminum complexes[16,17,18,19] or trifluoroborates[20,21,22,23,24,25,26,27,28] as non-carbon fluoride acceptors to afford one-step labeling of peptides. (i) limited stability and high lipophilicity of the organosiliconbased 18F-labeling blocks; (ii) specific pH requirement for trifluoroborate-based 18F-labeling; (iii) steric effect of bulky Al18F-based chelate synthons; and iv) potential biosafety issue due to possible metal contamination in the final product
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