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
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.
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
Christ Emanuel, Antwi Kwadwo, Fani Melpomeni, Wild Damian (2020), Innovative imaging of insulinoma: the end of sampling? A review., in Endocrine-related cancer
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.
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.
Antwi Kwadwo, Nicolas Guillaume, Wild Damian, Christ Emanuel (2019), Molecular imaging for neuroendocrine tumours, in Swiss Medical Weekly
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.
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
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.
Christ Emanuel (2016), Preface - Neuroendocrine tumours.
, 30(1), 1-1, Best Pract Res Clin Endocrinol Metab, Amsterdam 30(1), 1-1.
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.
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.
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.
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.