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[18F]GE-180 PET/CT assessment of enterocytic translocator protein (TSPO) over-expression: a pilot study in gastrointestinal GVHD

Bone Marrow Transplantation volume 57, pages 517–519 (2022)Cite this article

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Diagnostic endoscopy for suspected acute gastrointestinal graft-versus-host disease (GI-GVHD) is limited by procedural risk, GI tract length and patchy histological involvement. Consequently, up to one quarter of GI-GVHD cases lack histological confirmation [1], with implications for treatment and prognostication. Positron emission tomography combined with computed tomography (PET/CT) assessment of the entire GI tract could overcome the shortcomings of endoscopy but is limited by a lack of specificity of the 18-fluoro-deoxyglucose ([18F]FDG) radiotracer [2, 3]. The translocator protein 18 kDa (tryptophan-rich sensory protein oxygen sensor; TSPO) [4] is an outer mitochondrial membrane protein that is overexpressed by enterocytes in inflammatory bowel diseases (IBD) [5, 6] following tumour necrosis factor (TNF) and interleukin (IL)-8-driven reactive oxygen species (ROS) production and apoptosis [7]. We hypothesised that enterocytic TSPO expression is also increased during acute GI-GVHD and that it could serve as a biomarker for PET/CT imaging. Here, we report our analysis of enterocytic TSPO expression in tissue biopsies of GI-GVHD and results of a prospective pilot study of PET/CT using [18F]GE-180 (GE Healthcare, Chicago USA), an established third-generation high-affinity TSPO radiotracer [8], in adult recipients of allogeneic hematopoietic cell transplantation (HCT). This study was approved by the Metro North Human Research Ethics Committee (HREC/17/QRBW/216) and registered on anzctr.org.au, trials registration number ACTRN12617000933358.

Full study methods are detailed in the Supplementary Appendix. Between October 2017 and December 2018, eight patients with suspected new-onset GI-GVHD were prospectively enrolled. Baseline participant data are summarised in Supplementary Table 1. All participants underwent endoscopy within one day of presentation, and diagnostic [18F]GE-180 PET/CT within median one day (range 0–6 days) following endoscopy. [18F]GE-180 avidity in the stomach, small bowel, colon and rectum was rated visually compared to physiological background activity. The maximum standardised uptake value (SUVmax) was calculated and compared to reference tissues (liver, mediastinal blood pool [MBP] and bone marrow [BM]) and correlated with biopsy results. An overall “True Positive” [18F]GE-180 PET/CT was defined when a histologically confirmed GI-GVHD site demonstrated SUVmax exceeding that of reference tissue. Regardless of final diagnosis or clinical management, participants were also offered a repeat [18F]GE-180 PET/CT 7 days later to assess any potential correlation with clinical outcome.

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Fig. 1: TSPO overexpression in GI-GVHD.

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Acknowledgements

This research was approved by the Metro North Human Research Ethics Committee (HREC/17/QRBW/216), and was performed in accordance with the principles of the Declaration of Helsinki. Funding was provided by a RBWH Foundation Susan Suduk Diamond Care Grant and a Pathology Queensland research grant. All [18F]GE-180 PET/CT study participants freely gave written informed consent. Authority to access stored tissue samples was given under a waiver of consent by the Data Custodian of the Queensland Public Health Act. The [18F]GE-180 PET/CT study was prospectively registered with the Therapeutic Goods Administration of Australia (2017-CTN-03010) and the Australian New Zealand Clinical Trials Registry (ACTRN12617000933358). The authors wish to thank David Williams and RBWH BMT Ward 5C nursing staff for patient care during [18F]GE-180 PET/CT, Louise Campbell at HIRF, Melissa Latter and Marissa Bartlett at Q-TRaCE, Dr Andrea Henden for advice and support, and all patients who participated.

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Authors and Affiliations

  1. Department of Haematology and Bone Marrow Transplant, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Ashleigh P. Scott, Siok-Keen Tey & Glen A. Kennedy

  2. School of Medicine, The University of Queensland, Brisbane, QLD, Australia

    Ashleigh P. Scott, Paul Thomas, David A. Pattison, Siok-Keen Tey & Glen A. Kennedy

  3. Department of Nuclear Medicine and Specialised PET Services, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Paul Thomas & David A. Pattison

  4. Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia

    Leo Francis & Paula Ridge

  5. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Siok-Keen Tey

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Contributions

All authors contributed to study conceptualisation and design. [18F]GE-180 PET/CT study activities, including participant enrolment, performance of study activities and data collection, were performed by APS. [18F]GE-180 PET/CT analysis was performed by PT, DAP and APS. Anti-TSPO IHC was performed by PR, quantified by APS, and assessed by LF and APS. Analysis of all study data was performed by APS and reviewed by all authors. The manuscript was written by APS, and all authors commented on previous versions. All authors read and approved the final manuscript.

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Correspondence to Ashleigh P. Scott.

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Scott, A.P., Thomas, P., Pattison, D.A. et al. [18F]GE-180 PET/CT assessment of enterocytic translocator protein (TSPO) over-expression: a pilot study in gastrointestinal GVHD. Bone Marrow Transplant 57, 517–519 (2022). https://doi.org/10.1038/s41409-022-01571-3

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