Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[¹⁸F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([¹⁸F]FSA) as a novel aromatic sulfonamide-based click chemistry building block. [¹⁸F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [¹⁸F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [¹⁸F]F-SA as click chemistry building blockwas demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 %(HSA), and 25 %(L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for ¹⁸F labeling of biopolymers, Cu(I)-mediated click chemistry with [¹⁸F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter ¹⁸F.