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



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


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.


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.


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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  1. 1.

    Palestro CJ (2009) Radionuclides imaging of infection: in search of the grail. J Nucl Med 50:671–673

  2. 2.

    Corstens FHM, van der Meer JWM (1999) Nuclear medicine’s role in infection and inflammation. Lancet 354:765–7670

  3. 3.

    Kumar S, Basu S, Torigian D et al (2008) Role of modern imaging techniques for diagnoses of infection in the area of 18F-fluordeoxyglucose positron emission tomography. Clin Microbiol Rev 21:209–224

  4. 4.

    Langer O, Mitterhauser M, Brunner M, Zeitlinger M, Wadsak W, Mayer BX, Kletter K, Muller M (2003) Synthesis of [18F]ciprofloxacin for PET studies in humans. Nucl Med Biol 30:285–291

  5. 5.

    Langer O, Brunner M, Zeitlinger M et al (2005) In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging infection with PET. Eur J Nucl Med Mol Imaging 32:143–150

  6. 6.

    Sasser TA, Van AVermaete AE, White A et al (2013) Bacterial Infection Probes and Imaging Strategies in Clinical Nuclear Medicine and Preclinical Molecular Imaging. Current Topic. Med Chem 13:479–487

  7. 7.

    Petruzz IN, Shanthly N, Thakur M (2009) Recent trend in soft tissue infection imaging. Semin Nucl Med 39:115–123

  8. 8.

    Diaz LA, Foss CA, Thornton K et al (2007) Imaging of musculoskeletal bacterial infection by [124I]FIAU- PET/CT. PLoS ONE 2:e1007

  9. 9.

    Ning X, Lee S, Wang Z et al (2011) Maltodextrine-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nat Mater 10:602–607

  10. 10.

    Dahl MK, Manson MD (1985) interspecific reconstitution of maltose transport and chemotaxis in Escherichia coli with maltose binding protein from various enteric bacteria. J Bactriol 164:1037–1063

  11. 11.

    Gopal S, Berg D, Hagen N et al (2010) Maltose and maltodextrine utilization by listeria monocytogenes depend on an inducible ABC transporter which is repressed by glucose. PLoS ONE 5:e10349

  12. 12.

    Braitsch M, Kahlig H, Kontaxis G et al (2012) Synthesis of fluorinated maltose derivatives for monitoring protein interaction by 19 F NMR. Beilstein J Org Chem 8:448–455

  13. 13.

    Excoffier G, Gagnaire D, Utille J-P (1975) Coupure selective par 1 hydrozine des groupments acetyles anomeres de residus glycosyles acetyls. Carbohydr Res 39:368–373

  14. 14.

    Toshima K (2000) Glycosyl fluorides in glycosidations. Carbohydr Res 327:15–26

  15. 15.

    Lal GS, Pez GP, Pasaresi RJ et al (1999) Bis (2-methyl) aminosulfur trifluoride: a new broad spectrum deoxofluorinating agent with enhanced thermal stability. J Org Chem 64:7048–7054

  16. 16.

    Takeo K, Shinmitsu K (1984) A convenient synthesis of 6′-C-substituted b-maltose heptaacetates and of panose. Carbohydr Res 133:135–145

  17. 17.

    Ye S, Rezende MM, Deng W-P, Herbert B, Daly JW, Johnson RA, Kirk KL (2004) Synthesis of 2′, 5′-dideoxy-2-fluoroadenosine and 2′, 5′-dideoxy-2′,5′-difluoroadenosine: potent P-site inhibitors of adenylyl cyclase. J Med Chem 47:1207–1213

  18. 18.

    Best WM, Stick RV, Tilbrook DMG (1997) The synthesis of some epoxyalkyl-deoxyhalo-β-cellobiosides. Aust J Chem 50:13–18

  19. 19.

    Dutton GGS, Slessor KN (1966) Synthesis of 6′-Substituted Maltose. Cana J Chem 44:1069

  20. 20.

    De Castro KA, Rhee H (2008) Selective nosylation of 1-phenylpropane-1,3-diol and perchloric acid mediated Friedel-Crafts alkylation: key steps for the new and straightforward synthesis of Toletero dine. Synthesis No. 12 P: 1841–1844

  21. 21.

    Tyokuni T, Kumar JSD, Gunawan P et al (2004) Practical and reliable synthesis of 1, 3, 4, 6-tetra-O-acetyl-2-O-trifluoromethanesulffonyl-β-D-mannopyranosyl, a precursor of 2-deoxy-2-[18F]fluoro-D-glucose. Mol Imaging Biol 6:417

  22. 22.

    Young SJM, Weser E (1971) The metabolism of circulating maltose in man. J Clin Inves 50:986–9891

  23. 23.

    Ferenci T (1980) Methyl-α-maltoside and 5-thiomatose: analogs transported by escherichia coli maltose transported system. J Bacteriol 144:7–11

  24. 24.

    Carruthers A, DeZutter J, Ganguly A, Devaskar SU (2009) Will the original glucose transporter isoform please stand up! Am J Physiol Endocrinol Metab 297:E836–48

  25. 25.

    Gowrishankar et al (2014) Investigation of 6-[18F]fluoromaltose as a novel PET tracer for imaging bacterial infection. PLos One (accepted)

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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.

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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).

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Key words

  • Bacterial infection
  • Imaging
  • Positron emission tomography
  • Maltose