[ 11 C]PABA: A PET tracer targeting bacteria-specific metabolism Christopher A. Mutch 1 , Alvaro A. Ordonez 2 , Hecong Qin 1 , Matthew Parker 1 , Lauren E. Bambarger 2 , Javier E. Villanueva-Meyer 1 , Joseph Blecha 1 , Valerie Carroll 1 , Celine Taglang 1 , Robert Flavell 1 , Renuka Sriram 1 , Henry VanBrocklin 1 , Oren Rosenberg 3 , Michael A. Ohliger 1,4 , Sanjay K. Jain 2,* , Kiel D. Neumann 5,* , and David M. Wilson 1,* 1 Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA 2 Center for Infection and Inflammation Imaging Research, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA 3 Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA 4 Department of Radiology, Zuckerberg San Francisco General Hospital, San Francisco CA 94110, USA 5 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22903, USA Abstract 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 * Correspondence and Reprint Request: David Wilson, M.D., Ph.D., Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave., San Francisco, CA 94143, Phone: (415) 353-1668, Fax: (415) 353-8593, david.m.wilson@ucsf.edu. Kiel D. Neumann, Ph.D., Department of Radiology and Medical Imaging, University of Virginia, 480 Ray C. Hunt Dr., Charlottesville, VA 22903, Phone: (434) 243-1770, Fax: (434) 982-4149, kdn2e@virginia.edu. Sanjay K. Jain, Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II, Room 1.09, Baltimore, MD 21287, Phone: (410) 502-8241, Fax: (410) 614-8173, sjain5@jhmi.edu. Notes: The authors declare no competing financial or other interests. Supplementary information: Please see the supplementary information for detailed information regarding synthesis, and several in vitro and imaging studies not reported in the main text. Author contributions: DMW, SKJ and KN proposed and supervised the overall project. CM, KN, JVM, RS obtained in vitro data. CM, KN, LEB, VC, CT and JB performed or supported the radiochemistry. CM, JVM, RF, MP, DW performed μPET-CT imaging studies and subsequent data analysis. CM, JVM performed ex vivo analysis. CM, AO, DMW, KN, SKJ, HQ, JVM, HVB, RF, MO, OR wrote and edited the paper. HHS Public Access Author manuscript ACS Infect Dis. Author manuscript; available in PMC 2018 July 13. Published in final edited form as: ACS Infect Dis. 2018 July 13; 4(7): 1067–1072. doi:10.1021/acsinfecdis.8b00061. Author Manuscript Author Manuscript Author Manuscript Author Manuscript