18F-labelled gentiobiose as potential PET-radiotracer for specific bacterial imaging: precursor synthesis, radiolabelling and in vitro evaluation

Felicitas Landau; Sven Hermann; Sonja Schelhaas; Michael Schäfers; Silke Niemann; Andreas Faust

doi:10.1055/a-2365-8054

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2024; 63(05): 300-305
DOI: 10.1055/a-2365-8054

Original Article

¹⁸F-labelled gentiobiose as potential PET-radiotracer for specific bacterial imaging: precursor synthesis, radiolabelling and in vitro evaluation

¹⁸F-markierte Gentiobiose als potenzieller PET-Radiotracer für die spezifische Bildgebung bakterieller Infektionen: Precursorsynthese, Radiomarkierung und in vitro-Evaluation

Felicitas Landau

¹European Institute for Molecular Imaging, University of Münster, Münster, Germany (Ringgold ID: RIN9185)

²Department of Nuclear Medicine, University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Sven Hermann

¹European Institute for Molecular Imaging, University of Münster, Münster, Germany (Ringgold ID: RIN9185)

,

Sonja Schelhaas

¹European Institute for Molecular Imaging, University of Münster, Münster, Germany (Ringgold ID: RIN9185)

,

Michael Schäfers

¹European Institute for Molecular Imaging, University of Münster, Münster, Germany (Ringgold ID: RIN9185)

²Department of Nuclear Medicine, University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Silke Niemann

³Institute of Medical Microbiology, University Hospital Münster, Münster, Germany (Ringgold ID: RIN39069)

,

Andreas Faust

¹European Institute for Molecular Imaging, University of Münster, Münster, Germany (Ringgold ID: RIN9185)

› Author Affiliations

Abstract

Aim Bacterial infections are a clinical challenge, requiring fast and specific diagnosis to ensure effective treatment. Therefore, this project is dedicated to development of positron emission tomography (PET) radiotracers specifically targeting bacteria. Unlike previously developed bacteria-specific radiotracers, which are successful in detecting Gram-negative bacteria, tracers capable of imaging Gram-positive infections are still lacking.

Methods The disaccharide gentiobiose as abundant part of the cell wall of Gram-positive bacteria could fill this gap. Herein, the synthesis and evaluation of 2‘-deoxy-2‘-[¹⁸F]fluorogentiobiose ([¹⁸F]FLA280) is reported. The precursor for radiolabelling was obtained from a convergent synthesis under application of a benzylidene/benzyl group protecting strategy.

Results The first catalytic hydrogenation in ¹⁸F-radiochemistry is reported as proof of concept. The deprotection was carried out without any side product formation, giving the final radiotracer [¹⁸F]FLA280 in good radiochemical yield and excellent radiochemical purity. [¹⁸F]FLA280 was proven to be stable in murine and human blood serum for 120 minutes and was subjected to in vitro bacterial uptake studies towards S. aureus and E. coli resulting in a low bacterial uptake.

Conclusion The observed bacterial uptake indicates that [¹⁸F]FLA280 may be not a promising tracer candidate for in vivo translation and alternative candidates particularly for Gram-positive bacteria are required. However, further development on the concept of labelled carbohydrates and cell wall building blocks might be promising.

Keywords

18F-labelling - disaccharides - carbohydrate chemistry - bacterial imaging - PET

Full Text

References

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Supplementary Material

Supplementary Material