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

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 <i>in vitro</i> and <i>in vivo</i>. We found that <i>Staphylococcus aureus</i> (<i>S. aureus</i>) internalized [¹⁸F]MFTMT whereas <i>Escherichia coli</i> (<i>E. coli</i>) and CHO-K1 cells did not, in <i>in vitro</i>. Positron emission tomography imaging with [¹⁸F]MFTMT revealed that radioactivity accumulated not only in the <i>S. aureus</i>-infected group but also in the <i>E. coli</i>-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 <i>in vivo</i>. Similar to [¹⁸F]MFTMT, [¹⁸F]MFTM was internalized only by <i>S. aureus</i>. [¹⁸F]MFTM was identified as the only radioactive metabolite <i>in vivo</i>. 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 <i>in vitro</i>. 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.