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Currently, there exists no accurate, noninvasive clinical imaging method to detect living bacteria in vivo. Our goal is to provide a positron emission tomography (PET) method to image infection by ...

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 noninfectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabeled 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 st...

The differentiation of bacterial infection from other causes of inflammation is difficult in clinical practice and is critical where patient outcomes rely heavily on early interventions. In addition to physical exam and laboratory markers, several imaging modalities are frequently employed, but these techniques generally target the host immune response, rather than the living microorganisms themselves. Here, we describe a method to detect bacteria-specific metabolism using hyperpolarized (HP) 13C magnetic resonance spectroscopy. This technology allows visualization of the real-time conversion of enriched 13C substrates to their metabolic products, identified by their distinct chemical shifts. We have identified the rapid metabolism of HP [2-13C]pyruvate to [1-13C]acetate as a metabolic signature of common bacterial pathogens. We demonstrate this conversion in representative Gram-negative and Gram-positive bacteria, namely, Escherichia coli and Staphylococcus aureus, and its absence in key mammalian cell t...

The differentiation of bacterial infection from other causes of inflammation is difficult in clinical practice and is critical where patient outcomes rely heavily on early interventions. In addition to physical exam and laboratory markers, several imaging modalities are frequently employed, but these techniques generally target the host immune response, rather than the living microorganisms themselves. Here, we describe a method to detect bacteria-specific metabolism using hyperpolarized (HP) 13C magnetic resonance spectroscopy. This technology allows visualization of the real-time conversion of enriched 13C substrates to their metabolic products, identified by their distinct chemical shifts. We have identified the rapid metabolism of HP [2-13C]pyruvate to [1-13C]acetate as a metabolic signature of common bacterial pathogens. We demonstrate this conversion in representative Gram negative and Gram positive bacteria, namely Escherichia coli and Staphylococcus aureus, and its absence in key mammalian cell-types. Furthermore this conversion was successfully modulated in three mutant strains, corresponding to deletions of relevant enzymes.