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

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.