Site‐Selective, Late‐Stage C−H 18F‐Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

• Published in: Angewandte Chemie Vol. 130; no. 39; pp. 12915 - 12918
• Main Authors: Yuan, Zheliang, Nodwell, Matthew B., Yang, Hua, Malik, Noeen, Merkens, Helen, Bénard, François, Martin, Rainer E., Schaffer, Paul, Britton, Robert
• Format: Journal Article
• Language: English; Japanese
• Published: Weinheim Wiley Subscription Services, Inc 24-09-2018
• Subjects: 18F-Fluorierung; Chemical synthesis; Chemistry; Diagnostic systems; Fluorination; Fluorine isotopes; Labeling; Leucine; Medical imaging; Peptide; Peptides; PET-Bildgebung; Photokatalyse; Positron emission; Positron emission tomography; Radiomarkierung; Sodium; Tomography
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201806966

Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with 18F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [18F]‐N‐fluorobenzenesulfonimide effects site‐selective 18F‐fluorination at the branched position in leucine residues in unprotected and unaltered peptides. This streamlined process provides a means to directly convert native peptides into PET imaging agents under mild aqueous conditions, enabling rapid discovery and development of peptide‐based molecular imaging tools.
Ohne prosthetische Gruppe: Die Kombination von Natriumdecawolframat und [18F]‐N‐Fluorbenzolsulfonimid ermöglicht die regioselektive 18F‐Fluorierung an der Verzweigungsposition in Leucinresten in ungeschützten und unveränderten Peptiden. Dieser vereinfachte Prozess bietet die Möglichkeit, native Peptide direkt in Reagentien für die PET‐Bildgebung unter milden wässrigen Bedingungen zu überführen.