Fluorine-18 labelling of small interfering RNAs (siRNAs) for PET imaging

Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single‐stranded ribonucleic acids of short sequences, have been labelled with the positron‐emitter fluorine‐18 (T1/2: 109.8 min). The strategy involves (1) prosthetic conjugation of a single‐stranded oligonucleotide with [18F]FPyBrA (N‐[3‐(2‐[18F]fluoropyridin‐3‐yloxy)‐propyl]‐2‐bromoacetamide) followed by (2) formation of the target duplex by annealing with the complementary sequence, therefore, permitting parallel and combinatorial preparation of [18F]siRNAs. Pure fluorine‐18‐labelled siRNAs (0.55–1.11 GBq, specific activity: 74–148 GBq/µmol at EOB) could be obtained within 165 min starting from 37.0 GBq of starting [18F]fluoride (1.5–3.0%, non‐decay‐corrected isolated yields). Copyright © 2007 John Wiley & Sons, Ltd. Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single‐stranded ribonucleic acids of short sequences, have been labelled with the positron‐emitter fluorine‐18 (T1/2 : 109.8 min). The strategy involved, based on a prosthetic conjugation of one single‐stranded oligonucleotide with [18F]FPyBrA followed by formation of the target duplexes, proved to be compatible with half‐life of fluorine‐18 and permits parallel and combinatorial preparation of [18F]siRNAs. Copyright © 2007 John Wiley & Sons, Ltd.