TY - JOUR
T1 - Para-Aminobenzoic Acid
T2 - A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism
AU - Mutch, Christopher A.
AU - Ordonez, Alvaro A.
AU - Qin, Hecong
AU - Parker, Matthew
AU - Bambarger, Lauren E.
AU - Villanueva-Meyer, Javier E.
AU - Blecha, Joseph
AU - Carroll, Valerie
AU - Taglang, Celine
AU - Flavell, Robert
AU - Sriram, Renuka
AU - Vanbrocklin, Henry
AU - Rosenberg, Oren
AU - Ohliger, Michael A.
AU - Jain, Sanjay K.
AU - Neumann, Kiel D.
AU - Wilson, David M.
N1 - Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/7/13
Y1 - 2018/7/13
N2 - 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 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 showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.
AB - 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 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 showed that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.
KW - bacteria
KW - folate
KW - infection
KW - metabolism
KW - positron emission tomography
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UR - http://www.scopus.com/inward/citedby.url?scp=85046549853&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.8b00061
DO - 10.1021/acsinfecdis.8b00061
M3 - Article
C2 - 29712422
AN - SCOPUS:85046549853
SN - 2373-8227
VL - 4
SP - 1067
EP - 1072
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 7
ER -