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European Journal of Nuclear Medicine and Molecular Imaging

Open Access 22-04-2024 | Vancomycin | Original Article

Synthesis and preclinical evaluation of novel ¹⁸F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography

Authors: G. B. Spoelstra, S. N. Blok, L. Reali Nazario, L. Noord, Y. Fu, N. A. Simeth, F. F. A. IJpma, M. van Oosten, J. M. van Dijl, B. L. Feringa, W. Szymanski, P. H. Elsinga

Published in: European Journal of Nuclear Medicine and Molecular Imaging

Abstract

Introduction

Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three ¹⁸F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria.

Methods

[¹⁸F]FB-NHS and [¹⁸F]BODIPY-FL-NHS were conjugated to vancomycin. The resulting conjugates, together with our previously developed [¹⁸F]PQ-VE1-vancomycin, were tested for stability, lipophilicity, selective binding to Gram-positive bacteria, antimicrobial activity and biodistribution. For the first time, the pharmacokinetic properties of all three tracers were compared in healthy animals to identify potential binding sites.

Results

[¹⁸F]FB-vancomycin, [¹⁸F]BODIPY-FL-vancomycin, and [¹⁸F]PQ-VE1-vancomycin were successfully synthesized with radiochemical yields of 11.7%, 2.6%, and 0.8%, respectively. [¹⁸F]FB-vancomycin exhibited poor in vitro and in vivo stability and, accordingly, no bacterial binding. In contrast, [¹⁸F]BODIPY-FL-vancomycin and [¹⁸F]PQ-VE1-vancomycin showed strong and specific binding to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which was outcompeted by unlabeled vancomycin only at concentrations exceeding clinically relevant vancomycin blood levels. Biodistribution showed renal clearance of [¹⁸F]PQ-VE1-vancomycin and [¹⁸F]BODIPY-FL-vancomycin with low non-specific accumulation in muscles, fat and bones.

Conclusion

Here we present the synthesis and first evaluation of the vancomycin-based PET tracers [¹⁸F]BODIPY-FL-vancomycin and [¹⁸F]PQ-VE1-vancomycin for image-guided detection of Gram-positive bacteria. Our study paves the way towards real-time bacteria-targeted diagnosis of soft tissue and implant-associated infections that are oftentimes caused by Gram-positive bacteria, even after prophylactic treatment with vancomycin.

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Title: Synthesis and preclinical evaluation of novel 18F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography
Authors: G. B. Spoelstra
S. N. Blok
L. Reali Nazario
L. Noord
Y. Fu
N. A. Simeth
F. F. A. IJpma
M. van Oosten
J. M. van Dijl
B. L. Feringa
W. Szymanski
P. H. Elsinga
Publication date: 22-04-2024
Publisher: Springer Berlin Heidelberg
Keywords: Vancomycin
Positron Emission Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-024-06717-7

At a glance: The STEP trials

Springer Medicine

Synthesis and preclinical evaluation of novel ¹⁸F-vancomycin-based tracers for the detection of bacterial infections using positron emission tomography

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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