The role of [ 68 Ga]Ga-DOTATATE PET/CT in wild-type KIT / PDGFRA gastrointestinal stromal tumours (GIST)
Mendichovszky, Iosif A.
Challis, Ben G.
Hoopen, Rogier ten
Gallagher, Ferdia A.
Jones, Robin L.
Bulusu, Venkata Ramesh
Maher, Eamonn R.
Casey, Ruth T.
Springer Berlin Heidelberg
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Aloj, L., Giger, O., Mendichovszky, I. A., Challis, B. G., Ronel, M., Harper, I., Cheow, H., et al. (2021). The role of [ 68 Ga]Ga-DOTATATE PET/CT in wild-type KIT / PDGFRA gastrointestinal stromal tumours (GIST). EJNMMI Research, 11 (1)https://doi.org/10.1186/s13550-021-00747-0
Funder: GIST Support UK
Funder: NIHR Senior Investigator Award
Funder: European Research Council Advanced Researcher Award
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.
External DOI: https://doi.org/10.1186/s13550-021-00747-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316185