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 (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-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 14C 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-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] 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 [11C] 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 studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information, and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently there is significant overlap in the imaging appearance of infectious and non-infectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabelled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study we developed an efficient radiosynthesis for [11C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and shown that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.

A hyperpolarization technique using carbonate precursors of biocompatible molecules was found to yield high concentrations of hyperpolarized 13C bicarbonate in solution. This approach enabled large signal gains for low-toxicity hyperpolarized 13C pH imaging in a phantom and in vivo in a murine model of prostate cancer.