Localisation of occult extra‐pancreatic insulinoma using glucagon‐like peptide‐1 receptor molecular imaging

Mossman, Anna K.; Pattison, David A.; Hicks, Rodney J.; Hamblin, Peter S; Yates, Christopher J

doi:10.1111/imj.13664

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Methods with higher sensitivity are angiography with intraarterial calcium stimulation and venous sampling (ASVS), with a sensitivity of 85%, and endoscopic ultrasound (EUS), with a sensitivity of 74.8%. However, shortcomings of these methods are their invasive nature, with concomitant risk of complications, and that they are operator dependent . Since the majority of neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) at high levels, somatostatin receptor scintigraphy (SRS) with the radiolabeled peptide octreotide (binding SSTR subtypes 2 and 5) and its derivatives is a very efficient detection method .…”

Section: Preoperative Imaging Of Insulinomamentioning

confidence: 99%

“…However, shortcomings of these methods are their invasive nature, with concomitant risk of complications, and that they are operator dependent. 3,[9][10][11][12] Since the majority of neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) at high levels, somatostatin receptor scintigraphy (SRS) with the radiolabeled peptide octreotide (binding SSTR subtypes 2 and 5) and its derivatives is a very efficient detection method. 13,14 In benign insulinoma however, the receptor density of SSTR subtypes 2 and 5 is low, and therefore, sensitivity of SRS is relatively poor (<50%).…”

Section: Preoperative Imaging Of Insulinomamentioning

confidence: 99%

“…27 The [ 68 Ga]Ga-DO3A-VS-Cys40-exendin-4 tracer could be labeled with six times higher specific activity compared with Lys 40 (Ahx-DOTA-[ 68 Ga]Ga)NH2]-exendin-4, thereby enabling injection of lower peptide dose, and this tracer also showed good tumor uptake in INS-1 xenografts. 39 During the recent years, multiple case reports have been published in which 68 Ga-labeled exendin-4 tracers enabled successful detection of insulinomas with PET/CT, while other imaging methods were negative 11,[40][41][42][43][44] (for an overview of clinical PET tracers, see Table 4).…”

Section: Tracer Development and Clinical Implementationmentioning

confidence: 99%

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Exendin‐4 analogs in insulinoma theranostics

Jansen

Lith

Boss

et al. 2019

Labelled Comp Radiopharmac

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Insulinomas are neuroendocrine tumors arising from the pancreatic beta cells. Currently, surgical resection is the therapy of choice, and therefore, preoperative localization of insulinomas is essential. Nearly all insulinomas show overexpression of the glucagon‐like peptide‐1 receptor (GLP‐1R), and therefore, radiolabeled GLP‐1 peptide analog exendin‐4 can be used for diagnosis and preoperative localization with nuclear imaging. Here, we present an overview of the development and clinical implementation of exendin‐4–based tracers for single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging of insulinomas, and we address the potential use of this molecule for optical imaging. At last, we discuss the possibilities and pitfalls of the use of exendin‐4–based tracers for therapeutic applications such as peptide receptor radionuclide therapy (PRRT) or targeted photodynamic therapy (tPDT), giving a future outlook on the use of exendin‐4 in insulinoma theranostics.

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Section: Preoperative Imaging Of Insulinomamentioning

confidence: 99%

Section: Preoperative Imaging Of Insulinomamentioning

confidence: 99%

Section: Tracer Development and Clinical Implementationmentioning

confidence: 99%

See 1 more Smart Citation

Exendin‐4 analogs in insulinoma theranostics

Jansen

Lith

Boss

et al. 2019

Labelled Comp Radiopharmac

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“…Patient details are found in Tables 2 and S2. Exendin successfully localised an insulinoma (including an extra‐pancreatic site 20 ) in eight of nine patients (Figs 1,S1). All subsequently had surgical treatment.…”

Section: Resultsmentioning

confidence: 93%

Utility of ⁶⁸Ga‐DOTA‐Exendin‐4 positron emission tomography–computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia

Kalff

Iravani

Akhurst

et al. 2021

Internal Medicine Journal

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Background Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon‐like peptide‐1 receptors enabling positron emission tomography–computed tomography imaging with its radiolabelled analogue; 68Ga‐DOTA‐Exendin‐4 (Exendin). Aim To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non‐insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post‐gastric bypass hypoglycaemia (PGBH). Methods This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report. Results Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH. Conclusion In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH.

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Importance of localization of insulinomas: a systematic analysis

Burghardt

Meier

Uhl

et al. 2019

J Hepato Biliary Pancreat

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BackgroundProcedures suitable for preoperative localization of insulinomas are widely used but it is unclear whether they determine surgical success. We wanted to clarify whether preoperative localization or intraoperative ultrasound determines the success of surgically identifying and removing insulinomas.MethodsWe performed a systematic literature search (PubMed) yielding 100 publications with patient‐level data on preoperative localization procedures, intraoperative ultrasound, success of surgical identification and removal or single, benign insulinomas (published until 31 December 2016). The consequences of successful preoperative localization and intraoperative ultrasound for surgical identification and removal of an insulinoma could be analyzed for 863 and 529 patients with single benign insulinomas, respectively. Sensitivities of commonly employed methods to localize biochemically proven insulinomas were calculated for single benign (1,153 patients), multiple benign, and malignant insulinomas, also in relation to diameter and intra‐pancreatic location.ResultsThe success of surgery (identification and removal of single benign insulinomas) in patients with a biochemically proven insulinoma was high (approximately 98%) even in the absence of preoperative localization. However, successful preoperative localization or intraoperative ultrasonography slightly, but significantly, increased the probability of surgically identifying/removing single benign insulinomas (by 1.4% and 2.0%, P = 0.012 and 0.0032, respectively). Diagnostic sensitivities of localization procedures varied widely, with GLP‐1 receptor scintigraphy achieving the highest sensitivity despite its non‐invasive nature.ConclusionThe probability of surgically identifying and removing a single, benign insulinoma is high even in the absence of successful preoperative localization or intraoperative ultrasound. However, both approaches slightly, but significantly, improve the outcome to near 100%.

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Localisation of occult extra‐pancreatic insulinoma using glucagon‐like peptide‐1 receptor molecular imaging

Cited by 5 publications

References 7 publications

Exendin‐4 analogs in insulinoma theranostics

Exendin‐4 analogs in insulinoma theranostics

Utility of ⁶⁸Ga‐DOTA‐Exendin‐4 positron emission tomography–computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia

Importance of localization of insulinomas: a systematic analysis

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Localisation of occult extra‐pancreatic insulinoma using glucagon‐like peptide‐1 receptor molecular imaging

Cited by 5 publications

References 7 publications

Exendin‐4 analogs in insulinoma theranostics

Exendin‐4 analogs in insulinoma theranostics

Utility of 68Ga‐DOTA‐Exendin‐4 positron emission tomography–computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia

Importance of localization of insulinomas: a systematic analysis

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Utility of ⁶⁸Ga‐DOTA‐Exendin‐4 positron emission tomography–computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia