An efficient bioorthogonal strategy using CuAAC click chemistry for radiofluorinations of SNEW peptides and the role of copper depletion

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

The EphB2 receptor is known to be overexpressed in various types of cancer and is therefore a promising target for tumor cell imaging by positron emission tomography (PET). In this regard, imaging could facilitate the early detection of EphB2-overexpressing tumors, monitoring responses to therapy directed toward EphB2, and thus improvement in patient outcomes. We report the synthesis and evaluation of several fluorine-18-labeled peptides containing the SNEW amino acid motif, with high affinity for the EphB2 receptor, for their potential as radiotracers in the non-invasive imaging of cancer using PET. For the purposes of radiofluorination, EphB2-antagonistic SNEW peptides were varied at the C terminus by the introduction of L-cysteine, and further by alkyne- or azide-modified amino acids. In addition, two novel bifunctional and bioorthogonal labeling building blocks [(18)F]AFP and [(18)F]BFP were applied, and their capacity to introduce fluorine-18 was compared with that of the established building block [(18)F]FBAM. Copper-assisted Huisgen 1,3-dipolar cycloaddition, which belongs to the set of bioorthogonal click chemistry reactions, was used to introduce both novel building blocks into azide- or alkyne-modified SNEW peptides under mild conditions. Finally, the depletion of copper immediately after radiolabeling is a highly important step of this novel methodology.

Details

OriginalspracheEnglisch
Seiten (von - bis)935-945
Seitenumfang11
FachzeitschriftChemMedChem
Jahrgang8
Ausgabenummer6
PublikationsstatusVeröffentlicht - Juni 2013
Peer-Review-StatusJa

Externe IDs

Scopus 84878374005
ORCID /0000-0002-6432-5694/work/146644246

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Alkynes/chemistry, Amino Acids/chemistry, Animals, Azides/chemistry, Click Chemistry, Copper/chemistry, Cyclization, Fluorine Radioisotopes/chemistry, Male, Organometallic Compounds/chemical synthesis, Peptides/chemical synthesis, Positron-Emission Tomography, Radiopharmaceuticals/chemical synthesis, Rats, Rats, Wistar, Receptor, EphB2/antagonists & inhibitors, Structure-Activity Relationship