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Abstract
Background
[68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called ‘wild-type’ GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST.
Aims
To investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST.
Methods
[68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study.
Results
[68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST.
Conclusions
Our data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST.
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Details
1 University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cambridge University Hospitals Foundation Trust, Department of Nuclear Medicine, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386); Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.498239.d)
2 University of Cambridge, Department of Pathology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
3 Cambridge University Hospitals Foundation Trust, Department of Endocrinology, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
4 Cambridge University Hospitals Foundation Trust, Department of Nuclear Medicine, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
5 University of Cambridge, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
6 University of Cambridge, Department of Radiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.498239.d)
7 Cancer Research UK Cambridge Centre, Cambridge, UK (GRID:grid.498239.d)
8 Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Department of Medical Oncology, London, UK (GRID:grid.5072.0) (ISNI:0000 0001 0304 893X)
9 University College London Hospital Foundation Trust, Department of Medical Oncology, London, UK (GRID:grid.439749.4) (ISNI:0000 0004 0612 2754)
10 Cambridge University Hospitals Foundation Trust, Department of Medical Oncology, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386)
11 University of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre, Department of Medical Genetics, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
12 Cambridge University Hospitals Foundation Trust, Department of Endocrinology, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386); University of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre, Department of Medical Genetics, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)