The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

Luigi Aloj; Olivier Giger; Iosif A Mendichovszky; Ben G Challis; Meytar Ronel; Ines Harper; Heok Cheow; Rogier Ten Hoopen; Deborah Pitfield; Ferdia A Gallagher; Bala Attili; Mary McLean; Robin L Jones; Palma Dileo; Venkata Ramesh Bulusu; Eamonn R Maher; Ruth T Casey

doi:10.1186/s13550-021-00747-0

The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

Luigi Aloj, Olivier Giger, Iosif A Mendichovszky, Ben G Challis, Meytar Ronel, Ines Harper, Heok Cheow, Rogier Ten Hoopen, Deborah Pitfield, Ferdia A Gallagher, Bala Attili, Mary McLean, Robin L Jones, Palma Dileo, Venkata Ramesh Bulusu, Eamonn R Maher, Ruth T Casey

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	5
Journal	EJNMMI research
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s13550-021-00747-0
Publication status	Published - 14 Jan 2021

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Aloj, L., Giger, O., Mendichovszky, I. A., Challis, B. G., Ronel, M., Harper, I., Cheow, H., Hoopen, R. T., Pitfield, D., Gallagher, F. A., Attili, B., McLean, M., Jones, R. L., Dileo, P., Bulusu, V. R., Maher, E. R., & Casey, R. T. (2021). The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST). EJNMMI research, 11(1), Article 5. https://doi.org/10.1186/s13550-021-00747-0

@article{f465ba795bd14a779204852016fe7ad5,

title = "The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)",

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.",

author = "Luigi Aloj and Olivier Giger and Mendichovszky, {Iosif A} and Challis, {Ben G} and Meytar Ronel and Ines Harper and Heok Cheow and Hoopen, {Rogier Ten} and Deborah Pitfield and Gallagher, {Ferdia A} and Bala Attili and Mary McLean and Jones, {Robin L} and Palma Dileo and Bulusu, {Venkata Ramesh} and Maher, {Eamonn R} and Casey, {Ruth T}",

year = "2021",

month = jan,

day = "14",

doi = "10.1186/s13550-021-00747-0",

language = "English",

volume = "11",

number = "1",

}

Aloj, L, Giger, O, Mendichovszky, IA, Challis, BG, Ronel, M, Harper, I, Cheow, H, Hoopen, RT, Pitfield, D, Gallagher, FA, Attili, B, McLean, M, Jones, RL, Dileo, P, Bulusu, VR, Maher, ER & Casey, RT 2021, 'The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)', EJNMMI research, vol. 11, no. 1, 5. https://doi.org/10.1186/s13550-021-00747-0

TY - JOUR

T1 - The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

AU - Aloj, Luigi

AU - Giger, Olivier

AU - Mendichovszky, Iosif A

AU - Challis, Ben G

AU - Ronel, Meytar

AU - Harper, Ines

AU - Cheow, Heok

AU - Hoopen, Rogier Ten

AU - Pitfield, Deborah

AU - Gallagher, Ferdia A

AU - Attili, Bala

AU - McLean, Mary

AU - Jones, Robin L

AU - Dileo, Palma

AU - Bulusu, Venkata Ramesh

AU - Maher, Eamonn R

AU - Casey, Ruth T

PY - 2021/1/14

Y1 - 2021/1/14

N2 - 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.

AB - 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.

UR - https://ejnmmires.springeropen.com/articles/10.1186/s13550-021-00747-0

U2 - 10.1186/s13550-021-00747-0

DO - 10.1186/s13550-021-00747-0

M3 - Article

C2 - 33443647

SN - 2191-219X

VL - 11

JO - EJNMMI research

JF - EJNMMI research

IS - 1

M1 - 5

ER -

The role of [68 Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

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