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Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells ( 111 In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells ( 18 F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several  14 C D-amino acids for their incorporation into  E. coli  in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl- 11 C]methionine ([ 11 C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl- 11 C]methionine ([ 11 C] D-Met), and showed that it can rapidly and selectively differentiate both  E. coli  and  S. aureus  infections from sterile inflammation  in vivo . We believe that the ease of [ 11 C] D-Met radiosynthesis, coupled with its rapid and specific  in vivo  bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice.

Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers