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Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment—a prospective observational study

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Abstract

Background

Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure.

Patients and methods

HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5–5.0 MBq/kg of 18F-FDG.

Findings

One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma.

Interpretation

Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.

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Acknowledgements

Prof Sir Zumla and Prof Bomanji acknowledge support from the NIHR Biomedical Centre at UCL Hospitals Foundation NHS Trust. Sir Zumla holds an NIHR senior Investigator award and he is co-Principal Investigator of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET—https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation.

Role of funding source and oversight

The International Atomic Energy Agency (IAEA) aided in selection of recruitment centres with appropriate 18F-FDG PET/CT imaging facilities and funding for 18F-FDG PET/CT scans, consortium meetings and central facilities for data storage. None of the investigators received any payments.

Author information

Author notes

  1. Jamshed Bomanji, Rajnish Sharma, Bhagwant R. Mittal, Sanjay Gambhir, Ahmad Qureshy, Shamim M. F. Begum, Diana Paez, Mike Sathekge, Mariza Vorster, Dragana Sobic Saranovic, Pawana Pusuwan, Vera Mann, Sobhan Vinjamuri, Alimuddin Zumla and Thomas N. B. Pascual contributed equally to this work.

Authors and Affiliations

  1. Institute of Nuclear Medicine, 5th Floor, UCLH NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK

    Jamshed Bomanji & Vera Mann

  2. Division of Nuclear Medicine & PET Imaging, Specialist in Nuclear Medicine &Thyroid diseases, Molecular Imaging & Research Center (MIRC), INMAS, Delhi, India

    Rajnish Sharma

  3. Department of Nuclear Medicine & PET, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India

    Bhagwant R. Mittal

  4. Department of Nuclear Medicine, SGPGIMS, Rae Bareli Road, Lucknow, 226014, India

    Sanjay Gambhir

  5. Institute of Nuclear Medicine and Oncology (INMOL) Hospital, New Campus Road, Lahore, 54600, Pakistan

    Ahmad Qureshy

  6. National Institute of Nuclear Medicine & Allied Sciences (NINMAS), BSM Medical University Campus, 7th–10th Floor, Block-D, Shahbag, Dhaka, 1000, Bangladesh

    Shamim M. F. Begum

  7. Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, IAEA, Vienna, Austria

    Diana Paez

  8. Department of Nuclear Medicine, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa

    Mike Sathekge & Mariza Vorster

  9. Faculty of Medicine University of Belgrade and Center of Nuclear Medicine Clinical Center of Serbia, Belgrade, Serbia

    Dragana Sobic Saranovic

  10. Division of Nuclear Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok, 10700, Thailand

    Pawana Pusuwan

  11. Royal Liverpool University Hospital, Liverpool, L7 8XP, UK

    Sobhan Vinjamuri

  12. Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and the National Institute of Health Research Biomedical Research Centre at UCL Hospitals, London, UK

    Alimuddin Zumla

  13. Section of Nuclear Medicine and Diagnostic Imaging, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna International Centre, PO Box 100, 1400, Vienna, Austria

    Thomas N. B. Pascual

Authors
  1. Jamshed Bomanji
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  2. Rajnish Sharma
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  3. Bhagwant R. Mittal
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  6. Shamim M. F. Begum
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  7. Diana Paez
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  8. Mike Sathekge
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  9. Mariza Vorster
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  11. Pawana Pusuwan
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  12. Vera Mann
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  14. Alimuddin Zumla
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  15. Thomas N. B. Pascual
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Contributions

Jamshed Bomanji, Thomas NB Pascual and Alimuddin Zumla developed the concept and initiated discussions which led to the formation of the consortium. Rajnish Sharma, Bhagwant Rai Mittal, Sanjay Gambhir, Ahmad Qureshy, Shamim Momtaz Ferdousi Begum, Mike Sathekge, Mariza Vorster, Dragana Sobic Saranovic and Pawana Pusuwan led the study sites. Sobhan Vinjamuri conducted quality assessment of imaging data. Olga Morozova collated the CRFs. Vera Mann performed the data analyses. Jamshed Bomanji led the imaging studies and, with Alimuddin Zumla, Diana Paez and Thomas NB Pascual, developed the first and final drafts of the manuscript. All authors contributed to data interpretation and writing of the manuscript.

Corresponding author

Correspondence to Jamshed Bomanji.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

IAEA, Committee for Coordinated Research Activities, Nuclear Sciences and Applications (05-02-14). All procedures performed in participants were in accordance with ethical standards of the local institution and/or national research committee and in line with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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This article is part of the Topical Collection on Infection and inflammation.

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Bomanji, J., Sharma, R., Mittal, B.R. et al. Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment—a prospective observational study. Eur J Nucl Med Mol Imaging 47, 3118–3129 (2020). https://doi.org/10.1007/s00259-020-04888-7

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