Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

Christ, Emanuel; Wild, Damian; Ederer, Susanne; Béhé, Martin; Nicolas, Guillaume; Caplin, Martyn; Brändle, Michael; Clerici, Thomas; Fischli, Stefan; Stettler, Christoph; Ell, Peter J.; Seufert, Jochen; Gloor, Beat; Perren, Aurel; Reubi, Jean Claude; Forrer, Flavio

doi:10.1016/s2213-8587(13)70049-4

Cited by 162 publications

(167 citation statements)

References 24 publications

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“…Several series have described imaging findings consistent with nesidioblastosis (Christ et al 2013, Figure 5 A 59-year-old woman with endogenous hyperinsulinaemic hypoglycaemia referred for 68 Ga-DOTA-exendin-4 PET/CT for insulinoma localisation. Axial PET images (A) demonstrate focal intense uptake extending from the anterior margin of the left kidney (yellow circles), corresponding to an exophytic density arising from the pancreatic tail on fused PET/CT (B) and low dose CT (C) images.…”

Section: :6mentioning

confidence: 99%

“…The median reduction in the blood glucose level was 1.3 mmol/L (range 0.8-2.1 mmol/L) with a nadir occurring approximately 40 min after injection in a large series of patients imaged for insulinoma localisation with 111 In-exendin-4 (Christ et al 2013). Twenty of 30 patients in this study required exogenous glucose infusion for hypoglycaemia, whereas more recent studies (Antwi et al 2015, Luo et al 2016 routinely co-administer glucose infusion in all patients to minimise the risk of hypoglycaemia.…”

Section: :6mentioning

confidence: 99%

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Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Pattison¹,

Hicks²

2017

Endocrine-Related Cancer

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There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors (somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R)) the amine precursor uptake and decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[ 18 F]-l-fluoro-l-3,4-dihydroxyphenylalanine ( 18 F-FDOPA), and glycolytic metabolism with 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG). Accurate preoperative localisation and staging is critical to enable directed surgical excision or enucleation with minimal morbidity and preservation of residual pancreatic function. Benign insulinoma has near ubiquitous dense GLP-1R expression enabling accurate localisation with radiolabelled-exendin-4 compounds (e.g. 68 Ga-NOTA-exendin-4 PET/CT), whilst the rarer and more difficult to manage metastatic insulinoma typically express SSTR and is preferably imaged with radiolabelled-SSTR analogues such as 68 Ga-DOTA-octreotate (DOTATATE) PET/CT for staging and assessment of suitability for peptide receptor radionuclide therapy (PRRT). Similar to other metastatic neuroendocrine tumours, FDG PET/CT is used in the setting of highergrade metastatic insulinoma to provide important prognostic information that can guide treatment and determine suitability for PRRT. Interestingly, these three tracers appear to represent a spectrum of differentiation, which we conceptually describe as the 'tripleflop' phenomenon, with GLP-1R > SSTR > FDG in benign insulinoma and the opposite in higher-grade disease. This paper will review the clinical syndromes of adult hypoglycaemia (including a practical overview of the differential diagnoses to be considered), comparison of techniques for insulinoma localisation with emphasis on molecular imaging before discussing its implications for management of metastatic insulinoma.

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Section: :6mentioning

confidence: 99%

Section: :6mentioning

confidence: 99%

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Pattison¹,

Hicks²

2017

Endocrine-Related Cancer

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“…Furthermore, in a prospective multicentric study conducted by Christ et al,using 111 In-diethylenetriaminepentaacetic acid-exendin-4 for single-photon-emission CT examination, a transient exacerbation of hypoglycemia was reported (20). A large, prospective cohort study by Luo et al, using 68 Galabeled exendin-4 derivative, also showed promising sensitivity for PET/CT when compared to other imaging modalities.…”

Section: Discussionmentioning

confidence: 99%

“…GLP1 analogs have recently been shown to possess great sensitivity in the detection of insulinomas (20,21). Furthermore, in a prospective multicentric study conducted by Christ et al,using 111 In-diethylenetriaminepentaacetic acid-exendin-4 for single-photon-emission CT examination, a transient exacerbation of hypoglycemia was reported (20).…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of 18F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma

Nakuz

Berger

El-Rabadi

et al. 2018

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“…Conversely, malignant insulinomas often do express sst 2 , which can be targeted using SRS (24,60,61,62,63,64,65,66). In various studies, GLP1R scintigraphy using 111 In-DOTAexendin-4 successfully detected benign insulinomas (60,67,68,69,70). This radiopharmaceutical can also be successfully applied for the intraoperative localisation of these benign tumours (68).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs)

Herder¹

2014

European Journal of Endocrinology

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For patients with neuroendocrine tumours (NETs) of the gastrointestinal tract and pancreas (GEP) (GEP-NETs), excellent care should ideally be provided by a multidisciplinary team of skilled health care professionals. In these patients, a combination of nuclear medicine imaging and conventional radiological imaging techniques is usually mandatory for primary tumour visualisation, tumour staging and evaluation of treatment. In specific cases, as in patients with occult insulinomas, sampling procedures can provide a clue as to where to localise the insulin-hypersecreting pancreatic NETs. Recent developments in these fields have led to an increase in the detection rate of primary GEP-NETs and their metastatic deposits. Radiopharmaceuticals targeted at specific tumour cell properties and processes can be used to provide sensitive and specific whole-body imaging. Functional imaging also allows for patient selection for receptor-based therapies and prediction of the efficacy of such therapies. Positron emission tomography/computed tomography (CT) and single-photon emission CT/CT are used to map functional images with anatomical localisations. As a result, tumour imaging and tumour follow-up strategies can be optimised for every individual GEP-NET patient. In some cases, functional imaging might give indications with regard to future tumour behaviour and prognosis.

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Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

Abstract: Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Cited by 162 publications

References 24 publications

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Molecular imaging in the investigation of hypoglycaemic syndromes and their management

Clinical Value of 18F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma

GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs)

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