{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:51:29Z","timestamp":1792039889326,"version":"4.4.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"831","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI150684"],"award-info":[{"award-number":["R01AI150684"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-010245"],"award-info":[{"award-number":["INV-010245"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-027276"],"award-info":[{"award-number":["INV-027276"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:p>\n                    Early bactericidal activity and time to sputum conversion are well-established study end points in both preclinical animal models and clinical trials for testing drug regimens for pulmonary tuberculosis (TB). The development and optimization of treatment-shortening drug regimens for TB have been challenged by disparities between these study end points and nonrelapsing cure. We hypothesized that using lung lesions measured by 2-deoxy-2-[\n                    <jats:sup>18<\/jats:sup>\n                    F]fluoro-\n                    <jats:sc>d<\/jats:sc>\n                    -glucose\u2013positron emission tomography\/computed tomography (PET\/CT) imaging in infected marmosets could help to interpret treatment efficacies and better understand clinical treatment outcomes. Radiographic changes in lung lesions were measured using PET\/CT imaging in a cohort of infected marmosets, which were divided into 22 treatment arms (including monotherapies and combination drug treatments) for 2 months. We used unsupervised clustering to define multivariate treatment response profiles that combined quantitative changes in radiographic pathology and terminal bacterial burden per lung lesion to inform lesion-level responses to drug treatments. These drug response profiles not only aligned with known clinical outcomes but also provided lesion-level insights into clinical successes and failures. We found that the inferiority of the 4-month moxifloxacin-rifampicin-pyrazinamide-ethambutol regimen compared with the 6-month standard of care for individuals with lung cavitary TB could be predicted. The marmoset response profiles were matched to their respective histopathological classifications at necropsy and successfully distinguished cavitary granulomas that responded to treatment from cavitary granulomas that failed to improve or worsened after the first month of treatment. Our findings indicate that a combination of quantitative PET\/CT measures is more informative of TB treatment outcomes than bacterial burden.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ado9383","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:58:20Z","timestamp":1767812300000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["PET\/CT imaging of tuberculosis lung lesions in marmosets treated with different drug regimens aligns with human clinical outcomes"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2710-602X","authenticated-orcid":true,"given":"Talia","family":"Greenstein","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA."},{"name":"Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6074-9521","authenticated-orcid":true,"given":"Laura E.","family":"Via","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA."},{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0962-2620","authenticated-orcid":true,"given":"Mariana Pereira","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-7426","authenticated-orcid":true,"given":"Danielle M.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA."},{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel K.","family":"Dayao","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA."},{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7496-5218","authenticated-orcid":true,"given":"Ayan","family":"Abdi","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Fleegle","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Gomez","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1218-2508","authenticated-orcid":true,"given":"Katelyn M.","family":"Repoli","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Woodcock","sequence":"additional","affiliation":[{"name":"Tuberculosis Imaging Program, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-206X","authenticated-orcid":true,"given":"Helena I. M.","family":"Boshoff","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-4642","authenticated-orcid":true,"given":"Oluwaseun","family":"Egbelowo","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9002-8087","authenticated-orcid":true,"given":"Kamunkhwala","family":"Gausi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-079X","authenticated-orcid":true,"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-2065","authenticated-orcid":true,"given":"Firat","family":"Kaya","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4390-3555","authenticated-orcid":true,"given":"Matthew","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-6002","authenticated-orcid":true,"given":"Eric L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Tufts University School of Engineering, Medford, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9470-5009","authenticated-orcid":true,"given":"V\u00e9ronique A.","family":"Dartois","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA."},{"name":"Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2927-270X","authenticated-orcid":true,"suffix":"III","given":"Clifton E.","family":"Barry","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA."},{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-1424","authenticated-orcid":true,"given":"Bree B.","family":"Aldridge","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA."},{"name":"Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA."},{"name":"Department of Biomedical Engineering, Tufts University School of Engineering, Medford, MA, USA."},{"name":"Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12252"},{"key":"e_1_3_2_3_2","unstructured":"F. J. W.-M. Leong S. Eum L. E. Via C. E. 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L.","year":"2006","unstructured":"J. L. Johnson, D. J. Hadad, W. H. Boom, C. L. Daley, C. A. Peloquin, K. D. Eisenach, D. D. Jankus, S. M. Debanne, E. D. Charlebois, E. Maciel, M. Palaci, R. Dietze, Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 10, 605\u2013612 (2006).","journal-title":"Int. J. Tuberc. 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