Synthesis, radiolabeling, and biological evaluation of methyl 6-deoxy-6-[18F]fluoro-4-thio-α-d-maltotrioside as a positron emission tomography bacterial imaging agent

  • RSC Adv. 2025 Mar 21;15(11):8809-8829. doi: 10.1039/d5ra00693g.
Kiyoko Takemiya  1 ,  Wonewoo Seo  2  3 ,  Ronald J Voll  2  3 ,  Sheng Zhao  4 ,  Giji Joseph  1 ,  Shelly Wang  1 ,  Fanxing Zeng  2  3 ,  Jonathon A Nye  2  3  5 ,  Niren Murthy  4 ,  W Robert Taylor  1  6  7 ,  Mark M Goodman  2  3
Affiliations
  • 1. Division of Cardiology, Department of Medicine, Emory University School of Medicine 1750 Haygood Dr NE Atlanta Georgia 30322 USA [email protected].
  • 2. Department of Radiology and Imaging Sciences, School of Medicine, Emory University 1841 Clifton Road NE Atlanta Georgia 30322 USA.
  • 3. Center for Systems Imaging, Emory University 1364 Clifton Rd NE Atlanta Georgia 30022 USA.
  • 4. Department of Bioengineering, University of California at Berkeley Stanley Hall 306 Berkeley California 94720 USA.
  • 5. Department of Radiology and Radiological Science, Medical University of South Carolina 261 Calhoun Street Charleston South Carolina 29425 USA.
  • 6. Joseph Maxwell Cleland Atlanta VA Medical Center 1670 Clairmont Road Decatur Georgia 30033 USA.
  • 7. Wallace H. Coulter Department of Biomedical Engineering, School of Medicine, Emory University 1750 Haygood Dr NE Atlanta Georgia 30322 USA.
PMID: 40124918 DOI: 10.1039/d5ra00693g
Abstract

We developed fluorine-18 ([18F]) labeled methyl 6-deoxy-6-fluoro-4-thio-α-d-maltotrioside ([18F]MFTMT) for Bacterial imaging and evaluated its stability and efficacy in vitro and in vivo. We found that Staphylococcus aureus (S. aureus) internalized [18F]MFTMT whereas Escherichia coli (E. coli) and CHO-K1 cells did not, in in vitro. Positron emission tomography imaging with [18F]MFTMT revealed that radioactivity accumulated not only in the S. aureus-infected group but also in the E. coli-infected and non-infectious inflammation groups. Further studies revealed that rat serum digested [18F]MFTMT into [18F]-methyl 6-deoxy-6-fluoro-4-thio-α-d-maltoside ([18F]MFTM), while [18F]MFTMT was stable in human serum for 210 min. [18F]MFTM was identified as the only radioactive metabolite in vivo. Similar to [18F]MFTMT, [18F]MFTM was internalized only by S. aureus. [18F]MFTM was identified as the only radioactive metabolite in vivo. We found that the sodium-glucose co-transporter 1 (SGLT1) is expressed in inflammatory tissue, and SGLT1 overexpressing cells showed increased retention of [18F]MFTMT and [18F]MFTM in vitro. Our study showed that the thio-glycosyl bond is stable against enzymatic digestion, and maltotetraose or a longer maltodextrin backbone is desirable for bacteria-specific imaging to avoid nonspecific uptake by SGLT1.

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