A New Highly Reactive and Low Lipophilicity Fluorine-18 Labeled Tetrazine Derivative for Pretargeted PET Imaging

Outi Keinänen, Xiang-Guo Li, Naveen K. Chenna, Dave Lumen, Jennifer Ott, Carla F. M. Molthoff, Mirkka Sarparanta, Kerttuli Helariutta, Tapani Vuorinen, Albert D. Windhorst, Anu J. Airaksinen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

29 Citations (Scopus)

Abstract

A new F-18-labeled tetrazine derivative was developed aiming at optimal radiochemistry, fast reaction kinetics in inverse electron-demand Diels Alder cycloaddition (IEDDA), and favorable pharmacokinetics for in vivo bioorthogonal chemistry. The radiolabeling of the tetrazine was achieved in high yield, purity, and specific activity under mild reaction conditions via conjugation with 5-[F-18]fluoro-5deoxyribose, providing a glycosylated tetrazine derivative with low lipophilicity. The F-18-tetrazine showed fast reaction kinetics toward the most commonly used dienophiles in IEDDA reactions. It exhibited excellent chemical and enzymatic stability in mouse plasma and in phosphate-buffered saline (pH 7.41). Biodistribution in mice revealed favorable pharmacokinetics with major elimination via urinary excretion. The results indicate that the glycosylated F-18-labeled tetrazine is an excellent candidate for in vivo bioorthogonal chemistry applications in pretargeted PET imaging approaches.

Original languageEnglish
Pages (from-to)62-66
Number of pages5
JournalACS MEDICINAL CHEMISTRY LETTERS
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 2016
MoE publication typeA1 Journal article-refereed

Keywords

  • Bioorthogonal chemistry
  • click chemistry
  • kinetics
  • PET imaging
  • tetrazine
  • POSITRON-EMISSION-TOMOGRAPHY
  • PLASMA-PROTEIN BINDING
  • IN-VIVO CHEMISTRY
  • DRUG DISCOVERY
  • BIOORTHOGONAL CHEMISTRY
  • CLICK CHEMISTRY
  • PEPTIDE
  • CYCLOADDITION
  • STABILITY
  • LIGATION

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