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

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

doi:10.1007/s00259-024-06717-7

Cited by 5 publications

(4 citation statements)

References 63 publications

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“…The authors concluded that [ 18 F]pretomanid-PET is a promising agent for the noninvasive pretomanid concentration measurement of various tissues. (Spoelstra et al 2024) the highest accumulation in the spleen and high signals were also detected in the blood pool, with some accumulation in the kidneys and bladder.…”

Section: [ 18 F]pretomanidmentioning

confidence: 95%

“…The major pharmacological action of vancomycin is against Gram-positive bacteria. Spoelstra et al ( 2024 ) utilised these characteristics to synthesise and investigate three vancomycin-based tracers labelled with 18 F, i.e. [ 18 F]FB-vancomycin, [ 18 F]BODIPY-FL-vancomycin and [ 18 F]PQ-VE1-vancomycin (see Fig.…”

Section: Main Textmentioning

confidence: 99%

“…

Fig. 29 Structures of vancomycin, [ 18 F]FB-vancomycin, [ 18 F]BODIPY-FL-vancomycin and [ 18 F]PQ-VE1-vancomycin (Spoelstra et al 2024 ) …”

Section: Main Textmentioning

confidence: 99%

“…Conventional infection imaging agents (such as [ 67 Ga]Ga-citrate, [ 111 In]In-oxine- or [ 99m Tc]Tc-HMPAO-labelled leukocytes, and [ 18 F]FDG) do not target bacteria, but rather the host immune response to the bacterial infection, and will therefore also localise in sterile inflammatory foci. The nonspecificity of these tracers can result in delayed or even inaccurate diagnosis, localisation, and treatment of infection, which may increase the cost-related burden, antimicrobial resistance, morbidity and even mortality of patients (Jiang et al 2024 ; Margeta et al 2024 ; Santos et al 2024 ; Spoelstra et al 2024 ; Li et al 2020 ). The development and investigation of new radiopharmaceuticals focuses on the differentiation of infection from sterile inflammation and the imaging of specific infectious microbes and processes (Palestro 2019 ; Signore et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Recently developed radiopharmaceuticals for bacterial infection imaging

Kahts,

Summers,

Gutta

et al. 2024

EJNMMI radiopharm. chem.

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Background Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019. Main body Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [68Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [68Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [11C]para-aminobenzoic acid and D-methyl-[11C]-methionine, with clinical trials underway for [18F]fluorodeoxy-sorbitol, as well as for 11C- and 18F-labelled trimethoprim. Conclusion It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors’ opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents.

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Section: [ 18 F]pretomanidmentioning

confidence: 95%

Section: Main Textmentioning

confidence: 99%

“…

Fig. 29 Structures of vancomycin, [ 18 F]FB-vancomycin, [ 18 F]BODIPY-FL-vancomycin and [ 18 F]PQ-VE1-vancomycin (Spoelstra et al 2024 ) …”

Section: Main Textmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recently developed radiopharmaceuticals for bacterial infection imaging

Kahts,

Summers,

Gutta

et al. 2024

EJNMMI radiopharm. chem.

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Bacteria-targeted imaging using vancomycin-based positron emission tomography tracers can distinguish infection from sterile inflammation

Spoelstra,

Braams,

IJpma

et al. 2024

Eur J Nucl Med Mol Imaging

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Introduction Bacterial infections pose major challenges in medicine. To guide effective infection treatment, faster and more accurate diagnostic modalities are needed. Bacteria-targeted molecular imaging can meet these needs. The present study was aimed at the in vivo evaluation of two 18F-vancomycin-based PET tracers, for detection of deep-seated Gram-positive bacterial infections. These tracers were bench-marked against the current standard of care, [18F]FDG. Methods The potential of [18F]BODIPY-FL-vancomycin and [18F]PQ-VE1-vancomycin ([4+2]photocycloadduct of 9,10-phenanthrenequinone-vancomycin and [18F]fluorinated vinyl ether) to distinguish bacterial infections from sterile inflammation was evaluated in a murine myositis model. Tracer specificity was assessed by infecting mice either with the Gram-positive bacterium Staphylococcus aureus (n = 12) or the Gram-negative bacterium Escherichia coli (n = 12). The contralateral leg was injected with Cytodex beads to induce sterile inflammation, or with phosphate-buffered saline for control. In parallel, mice were imaged with [18F]FDG (n = 12). Dynamic positron emission tomography (PET) measurements, biodistribution analyses, and immunohistopathology were performed to determine tracer distribution and bacterial burden. Results Both 18F-vancomycin-PET tracers accumulated at sites of infection, but not at sites of sterile inflammation, in contrast to [18F]FDG. The tracers exhibited distinct biodistribution profiles, with [18F]BODIPY-FL-vancomycin being cleared more rapidly. Both 18F-vancomycin-PET tracers displayed significant target to non-target ratios of 2.95 for [18F]BODIPY-FL-vancomycin and 1.48 for [18F]PQ-VE1-vancomycin. Conclusion Vancomycin-based PET is a potentially attractive approach to distinguish Gram-positive bacterial infections from sterile inflammation.

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