title: PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.
abstract: Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Ray Y
authors.initials: RY
authors.lastname: Chen
authors.affiliation: Biostatistics Research Branch, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.affiliation: International Tuberculosis Research Center, Changwon 631-710, South Korea.
authors.forename: Myungsun
authors.initials: M
authors.lastname: Lee
authors.affiliation: NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Paripati
authors.affiliation: Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Mountz
authors.affiliation: National Masan Hospital, Changwon 631-710, South Korea.
authors.forename: Doosoo
authors.initials: D
authors.lastname: Jeon
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Zia
authors.affiliation: Division of Diagnostic Radiology, Clinical Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Homeira
authors.initials: H
authors.lastname: Zahiri
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Coleman
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Carroll
authors.affiliation: Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Department of Diagnostic Radiology, Pusan National University School of Medicine, Busan 609-735, South Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: PET Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.affiliation: NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.
authors.forename: Saher
authors.initials: S
authors.lastname: Lahouar
authors.affiliation: Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tartakovsky
authors.affiliation: Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosenthal
authors.affiliation: NET Esolutions Corporation (NETE), NETE-FGI Imaging Team, McLean, VA 22102, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Somaiyya
authors.affiliation: International Tuberculosis Research Center, Changwon 631-710, South Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Goldfeder
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.affiliation: National Masan Hospital, Changwon 631-710, South Korea.
authors.forename: Seung-Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: International Tuberculosis Research Center, Changwon 631-710, South Korea. Department of Microbiology and Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Institute of Infectious Disease and Molecular Medicine, and the Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch 7701, South Africa. cbarry@niaid.nih.gov.
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000328:Adult; D000465:Algorithms; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D064847:Multimodal Imaging; D015588:Observer Variation; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012372:ROC Curve; D011857:Radiographic Image Interpretation, Computer-Assisted; D012680:Sensitivity and Specificity; D012984:Software; D013183:Sputum / Q000382:microbiology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000000981:diagnostic imaging* / Q000628:therapy*
chemical_list: D019788:Fluorodeoxyglucose F18; D008795:Metronidazole