68Ga-Exendin-4 PET/CT Detects Insulinomas in Patients With Endogenous Hyperinsulinemic Hypoglycemia in MEN-1

Author:

Antwi Kwadwo1,Nicolas Guillaume12,Fani Melpomeni1,Heye Tobias1,Pattou Francois3,Grossman Ashley45,Chanson Philippe67,Reubi Jean Claude8,Perren Aurel8,Gloor Beat9,Vogt Deborah R10,Wild Damian12ORCID,Christ Emanuel211ORCID

Affiliation:

1. Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland

2. Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland

3. Department of General and Endocrine Surgery, Lille University Hospital, Lille France

4. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom

5. Neuroendocrine Unit, Royal Free Hospital, London, United Kingdom

6. Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

7. UMR S-1185, Université Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France

8. Department of Pathology, University of Bern, Bern, Switzerland

9. Department of Visceral Surgery, University Hospital of Bern, Inselspital, Bern, Switzerland

10. Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland

11. Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland

Abstract

Abstract Context Surgical intervention is advised in patients with multiple endocrine neoplasia type-1 (MEN-1) and nonfunctioning pancreatic neuroendocrine tumors (PanNETs) with a size ≥20 mm. Functioning PanNETs, such as in patients with endogenous hyperinsulinemic hypoglycemia (EHH) due to (one or multiple) insulinomas, should be treated surgically independent of size. Preoperative localization of insulinomas is critical for surgery. Objective To evaluate the feasibility and sensitivity of 68Ga-DOTA-exendin-4 positron emission tomography (PET)/CT in the detection of clinically relevant lesions in patients with MEN-1 and EHH in combination with MRI. Design Post hoc subgroup analysis of a larger prospective imaging study with 52 patients with EHH. Patients Six of 52 consecutive patients with EHH and genetically proven MEN-1 mutation were included. Interventions All patients received one 68Ga-DOTA-exendin-4 PET/CT and one MRI scan within 3 to 4 days. Thereafter, surgery was performed based on all imaging results. Main Outcome Measures Lesion-based sensitivity of PET/CT and MRI for detection of clinically relevant lesions was calculated. Readers were unaware of other results. The reference standard was surgery with histology and treatment outcome. True positive (i.e., clinically relevant lesions) was defined as PanNETs ≥20 mm or insulinoma. Results In six patients, 37 PanNETs were confirmed by histopathology. Sensitivity (95% CI) in the detection of clinically relevant lesions for combined PET/CT plus MRI, MRI, and PET/CT was 92.3% (64% to 99.8%), 38.5% (13.9% to 68.4%), and 84.6% (54.6% to 98.1%), respectively (P = 0.014 for the comparison of PET/CT plus MRI vs MRI). Postsurgery, EHH resolved in all patients. Conclusion 68Ga-DOTA-exendin-4 PET/CT is feasible in patients with MEN-1 and EHH. The combination with MRI is superior to MRI alone in the detection of insulinomas and may guide the surgical strategy.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Desirée og Niels Ydes Fond

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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