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Glukagon-like Peptide-1 Rezeptor Imaging in Patienten mit Insulinom und in Patienten nach autologer Beta-Zell Transplantation

English title Glucagon-like peptid-1 receptor (GLP-1R) imaging in patients with insulinomas and in patients after autologous beta cell transplantation
Applicant Christ Emanuel
Number 152938
Funding scheme Project funding (Div. I-III)
Research institution Poliklinik für Endokrinologie, Diabetologie und Klinische Ernährung Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Endocrinology
Start/End 01.06.2014 - 31.12.2017
Approved amount 372'000.00
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Keywords (10)

autologous beta cell transplantation; Positron emission tomography; 68Gallium; insulinoma; 111Indium; Glucagon-like peptid-1 receptor; Single photon emission tomography; Exendin-4; endogenous hyperinsulinemic hypoglycemia; beta cell mass

Lay Summary (German)

Lead
Der Nachweis von GLP-1 Rezeptoren bei der Lokalisation von Insulinomas und transplantierten Beta Zellen: Vergleich zwischen Szintigraphie und Positron-Emmissions-Tomographie
Lay summary

Diese Studie hat zwei Teile mit identischer Methode: 1) Die Lokalisation von gutartigen Insulinomen (ein Insulin sezernierender Tumor) und 2)die Quantifizierung von Beta-Zell-Masse (BCM). Die BCM entspricht allen Insulin produzierenden Zellen des Pankreas. BCM ist wichtig im Kontext von Patienten mit Typ1 und Typ2 Diabetes.

 

Insulinomas sind gutartige, kleine Tumoren der Bauchspeicheldrüse. Patienten mit Insulinoma leiden unter lebensbedrohlichen tiefen Blutzuckerspiegel. Die einzige Therapie ist die chirurgische Entfernung. Die Lokalisation ist eine Herausforderung, da 30% der Tumoren mittels MRI oder CT nicht entdeckt werden.

An der Oberfläche der Insulinoma gibt es GLP-1 Rezeptoren. Die Applikation eines Moleküls, das an diesen Rezeptor bindet und das mit einem Tracer verbunden ist (z.B. Szintigraphie), erlaubt die Lokalisation. Mit dieser Technik haben wir gezeigt, dass eine Lokalisation möglich ist. Diese Studie hier hat zum Ziel, die Szintigraphie mit der wahrscheinlich sensitiveren Methode der Positron Emission Tomographie (PET) zu vergleichen. Zusätzlich Vorteile der PET-Methode ist die kürzere Zeit bis zur Diagnose (4h vs <72h) und die geringere Radioaktivität.

Beta Zellen exprimieren GLP-1 Rezeptoren, wenn auch in geringeren Dichte als Insulinomas. Die Quantifizierung von BCM in vivo ist bis heute unmöglich, da keine verlässliche Methode verfügbar ist. In einem Pilot-Projekt werden Patienten mit T1D untersucht, denen Beta-Zellen in den Vorderarm transplantiert worden sind.

Wir glauben, dass die GLP-1 Rezeptor-Methode adäquat ist, Insulinoma zu lokalisieren resp. BCM zu quantifizieren. Dabei spekulieren wir, dass PET der konventionellen Szintigraphie überlegen ist.

Bei jedem Patienten werden beide Untersuchungen durchgeführt. Dabei entschiedet das Los, ob mit PET oder Szintigraphie gestartet wird.

Wir erwarten, dass wir mit den Resultaten dieser Studie eine praktikable Methode zur Lokalisation von Insulinomen, möglicherweise der BCM etablieren können.

Direct link to Lay Summary Last update: 04.04.2014

Lay Summary (English)

Lead
Glucagon-like peptide-1 receptor (GLP-1R) imaging in patients with insulinomas and in patients afterautologous beta cell transplantation
Lay summary

The study covers two parts with an identical methodology:1) the detection of benign insulinoma (an insulin secreting tumour) and 2)the determination of beta cell mass (BCM). The beta cells of the pancreas are the insulin producing cells of the pancreas. The BCM is important in type 1 diabetes (T1D) and type 2 (T2D).

Patients with insulinoma suffer from life-threatening low blood glucose levels. Insulinoma are small, benign tumours, located in the pancreas. The only curative approach is surgical excision. The detection remains a challenge since conventional imaging (MRI,CT)  cannot detect these tumours in ca.30% of the cases.

The surface of insulinoma exhibits GLP-1 receptors in high density. By administrating a molecule that target this receptor and that is linked to a tracer (i.e.scintigraphy), localization of insulinomas becomes possible. We have shown that the scintigraphy yielded promising results. The current study is designed to compare the scintigraphy with the probably more sensitive approach using Positron Emission Tomography (PET). Additional advantages of the PET methodology comprises a shorter time for the diagnosis (i.e. 4h vs up to 72h) and a reduced exposition to ionized radiation.

Bells cells also display GLP-1 receptors albeit in a lower density as insulinomas. The in vivo determination of BCM is currently impossible due to the lack of a reliable tool. In this project only a pilot study will be performed including patients with T1D that underwent beta cells transplantation in the forearm.

We hypothesize that GLP-1 receptor imaging is a valid methodology to localize small insulinoma and quantify transplanted BCM in humans. PET is more sensitive than scintigraphy.

Two studies with an identical protocol are planned: The patients are attributed by chance to start with the scintigraphy or with the PET.

We expect to establish a convenient methodology that allows the detection of small insulinomas. We aim at quantifying BCM after beta cell transplantation.

Direct link to Lay Summary Last update: 04.04.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Pitfalls in the Detection of Insulinomas With Glucagon-Like Peptide-1 Receptor Imaging.
Antwi Kwadwo, Hepprich Matthias, Müller Natasha A, Reubi Jean Claude, Fani Melpomeni, Rottenburger Christof, Nicolas Guillaume, Kaul Felix, Christ Emanuel R, Wild Damian (2020), Pitfalls in the Detection of Insulinomas With Glucagon-Like Peptide-1 Receptor Imaging., in Clinical nuclear medicine, 45(9), 386-392.
Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges
Refardt Julie, Hofland Johannes, Kwadwo Antwi, Nicolas Guillaume P., Rottenburger Christof, Fani Melpomeni, Wild Damian, Christ Emanuel (2020), Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges, in Reviews in Endocrine and Metabolic Disorders, x.
Innovative imaging of insulinoma: the end of sampling? A review.
Christ Emanuel, Antwi Kwadwo, Fani Melpomeni, Wild Damian (2020), Innovative imaging of insulinoma: the end of sampling? A review., in Endocrine-related cancer, 27.
68Ga-Exendin-4 PET/CT Detects Insulinomas in Patients With Endogenous Hyperinsulinemic Hypoglycemia in MEN-1
Antwi Kwadwo, Nicolas Guillaume, Fani Melpomeni, Heye Tobias, Pattou Francois, Grossman Ashley, Chanson Philippe, Reubi Jean Claude, Perren Aurel, Gloor Beat, Vogt Deborah R, Wild Damian, Christ Emanuel (2019), 68Ga-Exendin-4 PET/CT Detects Insulinomas in Patients With Endogenous Hyperinsulinemic Hypoglycemia in MEN-1, in The Journal of Clinical Endocrinology & Metabolism, 104(12), 5843-5852.
Volume Replacement Fluid Demarks Benign Insulinoma With 68Ga-DOTA-Exendin-4 PET/CT.
Antwi Kwadwo, Nicolas Guillaume, Fani Melpomeni, Christ Emanuel, Wild Damian (2019), Volume Replacement Fluid Demarks Benign Insulinoma With 68Ga-DOTA-Exendin-4 PET/CT., in Clinical nuclear medicine, 44(5), 347-348.
Molecular imaging for neuroendocrine tumours
Antwi Kwadwo, Nicolas Guillaume, Wild Damian, Christ Emanuel (2019), Molecular imaging for neuroendocrine tumours, in Swiss Medical Weekly, 149.
Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study
Antwi Kwadwo, Fani Melpomeni, Heye Tobias, Nicolas Guillaume, Rottenburger Christof, Kaul Felix, Merkle Elmar, Zech Christoph J., Boll Daniel, Vogt Deborah R., Gloor Beat, Christ Emanuel, Wild Damian (2018), Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT, SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study, in European Journal of Nuclear Medicine and Molecular Imaging, 45(13), 2318-2327.
Clinical presentation of 54 patients with endogenous hyperinsulinaemic hypoglycaemia: a neurological chameleon (observational study)
Valente Luca G., Antwi Kwadwo, Nicolas Guillaume P., Wild Damian, Christ Emanuel (2018), Clinical presentation of 54 patients with endogenous hyperinsulinaemic hypoglycaemia: a neurological chameleon (observational study), in Swiss Medical Weekly, 148.
Application of Ga(68) -DOTA-exendin-4 PET/CT to localize an occult insulinoma.
Cuthbertson DJ Banks M Khoo B Antwi K Christ E Campbell F Raraty M Wild D. (2016), Application of Ga(68) -DOTA-exendin-4 PET/CT to localize an occult insulinoma., in Clin Endocrinol , 84(5), 789-791.
Preface - Neuroendocrine tumours.
Christ Emanuel (2016), Preface - Neuroendocrine tumours., 30(1), 1-1, Best Pract Res Clin Endocrinol Metab, Amsterdam 30(1), 1-1.
Preoperative localization of adult nesidioblastosis using ⁶⁸Ga-DOTA-exendin-4-PET/CT
Christ E Wild D Antwi K Waser B Fani M Schwanda S Heye T Schmid C Baer HU Perren A Reubi J (2015), Preoperative localization of adult nesidioblastosis using ⁶⁸Ga-DOTA-exendin-4-PET/CT, in Endocrine, 50(3), 821-823.
Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.
Antwi K Fani M Nicolas G Rottenburger C Heye T Reubi JC Gloor B Christ E Wild D. (2015), Localization of Hidden Insulinomas with ⁶⁸Ga-DOTA-Exendin-4 PET/CT: A Pilot Study., in J Nucl Med, 56(7), 1075-1078.
Preoperative Glucagon-like peptide-1 receptor imaging reduces surgical trauma and pancreatic tissue loss in insulinoma patients: a report of three cases.
Wenning AS Kirchner P Antwi K Fani M Wild D Christ E Gloor B. (2015), Preoperative Glucagon-like peptide-1 receptor imaging reduces surgical trauma and pancreatic tissue loss in insulinoma patients: a report of three cases., in Patient Saf Surg, 2(9), 23.

Collaboration

Group / person Country
Types of collaboration
Endocrinology Departement Liege Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Professor Martyn E. Caplin, Neuroendocrine Unit, Royal Free Hospital, London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Dr. Thomas Clerici, Endocrine Surgery, Kantonalspital St.Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Endocrinolgy, University Hospital of Zurich, Prof. F. Beuschlein Switzerland (Europe)
- Industry/business/other use-inspired collaboration
Rotterdam, ENETS Center of Excellence Netherlands (Europe)
- Publication
- Exchange of personnel
Professor Beat Gloor, Department of Visceral Surgery, University Hospital of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Professor François Pattou, Head of Endocrine Surgery, University Hospital of Lille France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Professor Dr. Dr. Jochen Seufert, Universitätsklinikum Freiburg i.B. Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Professor Helmut Mäcke, Department of Nuclear Medicine, University Hospital Freiburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Endocrinology, Kantonsspital Aarau, Prof B Müller Switzerland (Europe)
- Publication
- Exchange of personnel
Médecine Nucléaire, Hopital Universitaire de Genève, Prof. M. Walter Switzerland (Europe)
- Publication
PD Dr. Chrisoph Henzen, Internal Medicine and Endocrinology, Kantonsspital Luzern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Professor Jean Claude Reubi, Experimental Pathology, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Professor Michael Braendle, Internal Medicine and Endocrinology, Kantonsspital St. Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Professor Aurel Perren, Department of Pathology, University Hospital of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Martin Behé, Center for Radiopharmaceutical Sciences ETH-PSI-USZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
COMBO Talk given at a conference Imaging in the Investigation of Hyoglycemic Syndromes 30.09.2019 Athens, Greece Christ Emanuel;
European Society of Endocrinology Talk given at a conference Innovative Imaging of insulinoma 14.05.2019 Lyon, France Christ Emanuel;
Société française d'endocrinologie (SFE) Talk given at a conference NEM-1 – nouvelle imagerie 06.05.2019 Lyon, France Christ Emanuel;
NET to go 2019 Talk given at a conference NET: new tracers 06.04.2019 Frankfurt, Germany Christ Emanuel;
Endocrinology update Talk given at a conference Pro Con Debate: Watchful waiting vs. therapy in NET 28.06.2018 Munich, Germany Christ Emanuel;
ENETS 2018 Talk given at a conference Case presentation 06.03.2018 Barcelona, Spain Christ Emanuel;
CAEK (Chirurgsche Arbeitsgemeinschaft endokrine Chirurgie) Talk given at a conference Interdisziplinarität im Management von NET – was steckt dahinter? Notwendigkeit oder Marketing 03.11.2017 Bern, Switzerland Christ Emanuel;
JADE - jung und Alt Talk given at a conference DOTATOC in a pituitary case 27.10.2017 Würzburg, Germany Christ Emanuel;
Journée Universitaire Paris Sud 2017 Talk given at a conference Scintigraphie au GLP-1 pour localiser les insulinomes 22.09.2017 Paris, France Christ Emanuel;
Nuklearmedizin 2017 Talk given at a conference Localisation of benign Insulinomas using Glucagon-like Peptide-1 Receptor (GLP-1R) SPECT/CT and PET/CT in a prospective clinical study 18.04.2017 Dresden, Germany Christ Emanuel; Del Pozzo Luigi; Wild Damian; Fani Melpomeni; Mansi Rosalba;
ENDO 2017 Talk given at a conference Localization of benign Insulinomas using Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT and PET/CT and MRI in a prospective clinical study 31.03.2017 Orlando, United States of America Wild Damian; Christ Emanuel; Baumann Tobias; Mansi Rosalba; Fani Melpomeni;
Deutsche Gesellschaft für Endokrinologie 2017 Talk given at a conference Finding the needle in the haystack - GLP-1 receptor imaging in endogenous hyperinsulinemic hypoglycemia 15.03.2017 Würzburg, Germany Fani Melpomeni; Christ Emanuel; Del Pozzo Luigi; Wild Damian; Mansi Rosalba; Reichmann Jan;
14th Annual ENETS Conference 2017 Poster Sensitivity of Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT, PET/CT and MRI for the localization of benign insulinoma: interims analysis of a prospective imaging efficacy study 08.03.2017 Barcelona, Spain Christ Emanuel; Wild Damian; Fani Melpomeni; Del Pozzo Luigi; Waser Beatrice;
Scientific exchange 2017 Talk given at a conference 111Ind-Exendin-4 SPECT/CT vs 68Ga-Exendin-4 PET/CT vs 3T MRI in patients with endogenous hyperinsulinemic hypoglycemiaLocalisation of Insulinomas - Preliminary results of a prospective clinical study 16.02.2017 Graz, Austria Christ Emanuel; Baumann Tobias; Wild Damian;
NET to go Talk given at a conference Tumorboard Discussion 03.02.2017 Frankfurt, Germany Christ Emanuel;
Tag der klinischen Forschung Universitätsspital Basel 2017 Talk given at a conference Localisation of Insulinomas through Glucagon-like Peptide-1 Receptor (GLP-1R) PET/CT and SPECT/CT in comparison with ce 3T MRI 19.01.2017 Basel, Switzerland Wild Damian; Fani Melpomeni;
Société Française d'Endocrinologie 2016 Talk given at a conference Imagerie des récepteurs du GLP-1 dans l'exploration des secrétions inappropriées d'insuline 05.10.2016 Bordeaux, France Mansi Rosalba; Wersinger Virginie; Del Pozzo Luigi; Wild Damian; Fani Melpomeni; Baumann Tobias; Christ Emanuel; Waser Beatrice;
RENATEN (Réseau nationale de prise en charge des tumeurs neuroendocrines) 2016 Talk given at a conference Hypoglycémie hyperinsulinémique endogène – nouvelle imagerie 13.09.2016 Lyon, France Waser Beatrice; Mansi Rosalba; Fani Melpomeni; Wild Damian; Christ Emanuel; Del Pozzo Luigi;
Society of nuclear medicine and molecular imaging 2016 Talk given at a conference Localization of benign Insulinomas using Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT and PET/CT in a prospective clinical study 11.06.2016 San Diego, United States of America Christ Emanuel; Baumann Tobias; Wild Damian; Mansi Rosalba; Fani Melpomeni;
European Congress of Endocrinology 2016 Poster Glucagon-like-1 Receptor imaging specifically localizes insulinomas in patients with Multiple Endocrine Neoplasia Type 1 (MEN-1) 28.05.2016 München, Germany Wild Damian; Fani Melpomeni; Christ Emanuel; Del Pozzo Luigi; Baumann Tobias; Wersinger Virginie; Mansi Rosalba;
D-A-CH Tagung der DGE, OEGS, SGED 2016 Poster Localization of benign Insulinomas using Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT and PET/CT in a prospective clinical study 25.05.2016 München, Germany Fani Melpomeni; Waser Beatrice; Wersinger Virginie; Baumann Tobias; Del Pozzo Luigi; Mansi Rosalba; Christ Emanuel; Wild Damian;
ENDO 2016 Talk given at a conference GLP-1Receptor imaging specifically localizes insulinomas in patients with MEN-1 01.04.2016 Boston, United States of America Del Pozzo Luigi; Waser Beatrice; Fani Melpomeni; Wersinger Virginie; Christ Emanuel; Wild Damian; Mansi Rosalba; Baumann Tobias;
European Congress of Endocrinology 2015 Poster Localisation of Insulinoma: Comparison of Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT, PET/CT and MRI. Preliminary results of a prospective clinical study. 16.05.2015 Dublin, Ireland Waser Beatrice; Christ Emanuel; Fani Melpomeni; Mansi Rosalba; Wild Damian; Baumann Tobias;
12th Annual ENETS Conference 2015 Talk given at a conference Localisation of Insulinoma and Beta-Cells: Comparison of Glucagon-Like Peptide-1 Receptor (GLP1-R) SPECT/CT, PET/CT and MRI. Preliminary Results of a Prospective Clinical Study 11.03.2015 Barcelona, Spain Wild Damian; Fani Melpomeni; Christ Emanuel; Waser Beatrice; Baumann Tobias;
ENDO 2015 Talk given at a conference Novel Imaging Procedure for the Localisation of Insulinoma using Glucagon-like Peptide-1 Receptor (GLP-1) PET/CT 05.03.2015 San Diego, United States of America Wild Damian; Waser Beatrice; Mansi Rosalba; Christ Emanuel; Baumann Tobias; Fani Melpomeni;
Wissenschaftliche Tagung der Schweizerisachen Gesellschaft für Endokrinologie und Diabetologie 2014 Talk given at a conference Comparison of GLP-1 Receptor SPECT/CT, PET/CT and MRI for the Localisation of Insulinoma and Beta-Cells – a prospective clinical study 27.11.2014 Bern, Germany Fani Melpomeni; Waser Beatrice; Del Pozzo Luigi; Baumann Tobias; Christ Emanuel; Wild Damian; Wersinger Virginie; Mansi Rosalba;
Arbeitstagung der Chirurgischen Arbeitsgemeinschaft Endokrinologie 2014 Talk given at a conference "All in one" GLP-1 receptor targeting in insulinoma 20.11.2014 Basel, Switzerland Wild Damian; Christ Emanuel; Fani Melpomeni; Waser Beatrice;


Awards

Title Year
Servier Forschungspreis 2015 2015
Bernard Delaloye Preis der Schweizerischen Gesellschaft für Nuklearmedizin 2014
Bester Kongressvortrag am SGR/SGNM Jahreskongress 2014 2014

Associated projects

Number Title Start Funding scheme
175544 A comparison of two novel molecular targeting systems for diagnosis and therapy in patients with medullary thyroid carcinoma (MTC) 01.01.2018 Project funding (Div. I-III)

Abstract

BackgroundInsulinoma: Insulinoma are rare, small insulin secreting neuroendocrine tumors. The only curative approach is the surgical excision. The detection remains a challenge and there is a need for a non-invasive, highly sensitive tool in localizing the insulinomas in the preoperative work-up. To this aim Glucagon-like peptide-1 receptor (GLP-1R) imaging (Single Photon Emission Computer Tomography co-registered with a CT; SPECT/CT) could be a convenient tool. The possibly more sensitive approach of targeting GLP-1R using Positron Emission Tomography (PET/CT) methodology has not been investigated in patients so far.Beta cell mass (BCM): The in vivo determination of BCM is currently impossible due to the lack of a reliable tool. Quantitative assessment of BCM in vivo is of enormous interest for patients with type 1 (T1D) and type 2 diabetes mellitus (T2D) in order to evaluate pathophysiological mechanisms of T1D and T2D and potential therapeutical interventions aiming at the prevention of autoimmune beta cell destruction (i.e. in T1D before clinical diagnosis or after islets transplantation) or preservation of BCM in T2D. Radionuclide-based methodology (GLP-1R imaging) using radioligands that directly target beta cells appears particularly promising.Quantitative PET is a powerful tool in clinical practice. In SPECT, quantification is more challenging. In Basel there is one of the first system (Symbia Intevo from Siemens) that includes all features for quantitative SPECT imaging. For the first time it will be possible to quantitatively compare the two methodologies (PET/CT and SPECT/CT) using an identical ligand.Working Hypothesis: Insulinoma Study and BCM Study•GLP-1R imaging using labelled exendin-4 is a valid methodology to localize small insulinoma and quantify transplanted beta cells in humans. PET/CT methodology is more sensitive than SPECT/CT.•Insulinoma uptake quantification will reduce interobserver variability.Specific Aims•To compare quantitative 111In-DOTA-exendin-4 SPECT/CT and quantitative 68Ga-DOTA-exendin-4 PET/CT for the preoperative localization of insulinomas in an intra-patient comparison. Gold standard is the histological diagnosis.•To quantitatively compare BCM-to-background uptake ratio in patients after autologous islets transplantation in the skeletal muscle of the forearm using 111In-DOTA-exendin-4 and 68Ga-DOTA-exendin-4. Experimental DesignTwo studies with an identical protocol are planned: 1) for patients with biochemical evidence of endogenous hyperinsulinemic hypoglycemia (n=32) and 2) for patients after beta cell transplantation (n=6, pilot study). The study (insulinoma and beta cell mass) includes a prospective, randomized, single-center protocol with a cross-over design. Group A will start with 68Ga-DOTA-exendin-4 PET/CT imaging followed by 111In-DOTA-exendin-4 SPECT/CT whereas Group B will be investigated in the inverse order. 111In-DOTA-exendin-4 has been administered to humans whereas the tracer 68Ga-DOTA-exendin-4 is used for the first time. Expected Value1.The establishment of a convenient non-invasive methdology that allows the detection of small insulionomas and eventually quantification of functional BCM in vivo using PET/CT. 2.The quantitative assessment of SPECT and PET will allow to calculate the respective receiver operating characteristics, sensitivitiy, specificity and diagnostic odds ratio for both Nuclear Medicine imaging modalities.
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