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Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

Abstract

Purpose

To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections.

Procedures

It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined.

Results

A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (∼96 % intact compound after 1-h and ∼65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose.

Conclusion

We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake experiments in E. coli and stability studies suggest a possible application of 6-[18F]fluoromaltose as a new PET imaging agent for visualization and monitoring of bacterial infections.

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Acknowledgments

This work was supported, in part, by NCI In vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747 (SSG). We also thank the cyclotron facility at Stanford for [18F]fluoride production and modification of a GE TRACERlab FX-FN synthetic module for radiosynthesis.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Correspondence to Sanjiv S Gambhir.

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Namavari, M., Gowrishankar, G., Hoehne, A. et al. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection. Mol Imaging Biol 17, 168–176 (2015). https://doi.org/10.1007/s11307-014-0793-5

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Key words

  • Bacterial infection
  • Imaging
  • Positron emission tomography
  • Maltose