4-[18F]Fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([18F]F-SA): a versatile building block for labeling of peptides, proteins and oligonucleotides with fluorine-18 via Cu(I)-mediated click chemistry
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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 ([ 18 F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ 18 F]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 [ 18 F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ 18 F]F-SA as click chemistry building block was 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 [ 18 F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter 18F.
KeywordsCu(I)-mediated click chemistry Fluorine-18 Peptides Proteins Oligonucleotides Positron emission tomography (PET)
The authors are grateful to Mareike Barth, Inge Közle, Stephan Preusche and Tilow Krauss for their excellent technical assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
- de Bruin B, Kuhnast B, Hinnen F, Yaouancq L, Amessou M, Johannes L, Samson A, Boisgard R, Tavitian B, Dollé F (2005) 1-[3-(2-[18F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione: design, synthesis, and radiosynthesis of a new [18F]fluoropyridine-based maleimide reagent for the labeling of peptides and proteins. Bioconjug Chem 16:406–420PubMedCrossRefGoogle Scholar
- Enas JD, Clark RD, VanBrocklin HF (1997) Synthesis of [18-F]RS-15385-FPh: a Potent And Selective Alpha-2 Adrenergic Receptor Ligand. J Label Compd Radiopharm 40:628–630Google Scholar
- Guhlke S, Wester HJ, Bruns C, Stöcklin G (1994) (2-[18F]fluoropropionyl-(D)phe1)-octreotide, a potential radiopharmaceutical for quantitative somatostatin receptor imaging with PET: synthesis, radiolabeling, in vitro validation and biodistribution in mice. Nucl Med Biol 21:819–825PubMedCrossRefGoogle Scholar
- Kolthoff IM (1925) A new set of buffer mixtures that can be prepared without the use of standardized acid or base. J Bio Chem 63:135–141Google Scholar
- Kostikov AP, Chin J, Orchowski K, Niedermoser S, Kovacevic MM, Aliaga A, Jurkschat K, Wängler B, Wängler C, Wester HJ, Schirrmacher R (2012) Oxalic acid supported Si-18F-radiofluorination: one-step radiosynthesis of N-succinimidyl 3-(di-tert-butyl[18F]fluorosilyl)benzoate ([18F]SiFB) for protein labeling. Bioconjug Chem 23:106–114PubMedCrossRefGoogle Scholar
- Liu S, Shen B, Chin FT, Cheng Z (2011) Recent progress in radiofluorination of peptides for PET molecular imaging. Curr Org Chem 8:584–592Google Scholar
- Shiue CY, Shiue GG, Bernard F, Greenberg JH (1999) Comparative studies of F-18 labeled benzamides and arylsulfonamides as sigma receptor ligands. J Label Compd Radiopharm 42:S108–S110Google Scholar
- Tavitian B (2003) In vivo imaging with oligonucleotides for diagnosis and drug development. Gut 52(Suppl 4):iv40–iv47Google Scholar