Distributable, Metabolic PET Reporting of Tuberculosis.

Autor:	Naseer Khan RM; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK., Ahn YM; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Marriner GA; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Via LE; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA.; Tuberculosis Imaging Program, DIR, NIAID, NIH, Bethesda, MD 20892.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., D'Hooge F; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK., Lee SS; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK.; School of Chemistry, University of Southampton, Southampton, UK., Yang N; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK.; The Rosalind Franklin Institute, Oxfordshire, OX11 0FA, UK., Basuli F; Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, MD USA., White AG; Department of Microbiology and Molecular Genetics, University of Pittsburgh., Tomko JA; Department of Microbiology and Molecular Genetics, University of Pittsburgh., Frye LJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh., Scanga CA; Department of Microbiology and Molecular Genetics, University of Pittsburgh., Weiner DM; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Sutphen ML; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Schimel DM; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Dayao E; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA., Piazza MK; Tuberculosis Imaging Program, DIR, NIAID, NIH, Bethesda, MD 20892., Gomez F; Tuberculosis Imaging Program, DIR, NIAID, NIH, Bethesda, MD 20892., Dieckmann W; Positron Emission Tomography Department, Clinical Center, NIH, Bethesda, MD USA 20892., Herscovitch P; Positron Emission Tomography Department, Clinical Center, NIH, Bethesda, MD USA 20892., Mason NS; Department of Radiology, University of Pittsburgh., Swenson R; Chemistry and Synthesis Center, NHLBI, NIH, Bethesda, MD USA., Kiesewetter DO; Molecular Tracer and Imaging Core Facility, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892., Backus KM; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK., Geng Y; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK., Raj R; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK., Anthony DC; Laboratory of Experimental Neuropathology, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK., Flynn JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh., Barry CE 3rd; Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD USA.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Davis BG; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK.; The Rosalind Franklin Institute, Oxfordshire, OX11 0FA, UK.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 03. Date of Electronic Publication: 2023 Apr 03.
DOI:	10.1101/2023.04.03.535218
Abstrakt:	Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [ 18 F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis ( Mtb ) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[ 18 F]fluoro-2-deoxytrehalose ([ 18 F]FDT) - can act as a mechanism-based enzyme reporter in vivo. Use of [ 18 F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb -specific processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [ 18 F]FDT from the most globally-abundant organic 18 F-containing molecule, [ 18 F]FDG. The full, pre-clinical validation of both production method and [ 18 F]FDT now creates a new, bacterium-specific, clinical diagnostic candidate. We anticipate that this distributable technology to generate clinical-grade [ 18 F]FDT directly from the widely-available clinical reagent [ 18 F]FDG, without need for either bespoke radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer. Competing Interests: Competing interests: The authors report no competing interests.
Databáze:	MEDLINE
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