68Ga-exendin-4 PET/CT detects insulinomas in patients with endogenous hyperinsulinemic hypoglycemia in MEN-1.

CONTEXT Surgical intervention is advised in patients with multiple endocrine neoplasia type-1 (MEN-1) with non-functioning pancreatic neuroendocrine tumors (PanNET) and a size ≥20mm. Functioning PanNET such as patients with endogenous hyperinsulinemic hypoglycemia (EHH) due to (one or multiple) insulinoma(s) should be treated surgically independent of size. Preoperative localization of insulinomas is critical for surgery. OBJECTIVE To evaluate feasibility and sensitivity of 68Ga-DOTA-exendin-4 PET/CT in the detection of clinical-relevant lesions in MEN-1 patients with EHH in combination with MRI. DESIGN Post-hoc subgroup-analysis of a larger prospective imaging study with 52 EHH patients. 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 3-4 days. Thereafter, surgery was performed based on all imaging results. MAIN OUTCOME MEASURES Lesion-based sensitivity of PET/CT and MRI for detection of clinical-relevant lesions was calculated. Readers were unaware of other results. Reference standard was surgery with histology and treatment outcome. True positive (=clinical-relevant lesions) was defined as PanNET ≥20mm or insulinoma. RESULTS In six patients, 37 PanNET were confirmed by histopathology. Sensitivity (95% confidence interval) in the detection of clinical-relevant lesions for combined PET/CT+MRI, MRI and PET/CT was 92.3% (64%-99.8%), 38.5% (13.9-68.4%) and 84.6% (54.6-98.1%), respectively (P-value=0.014 for the comparison of PET/CT+MRI versus MRI). Post-surgery, EHH resolved in all patients. CONCLUSION 68Ga-DOTA-exendin-4 PET/CT is feasible in MEN-1 patients with EHH. The combination with MRI is superior to MRI alone in the detection of insulinomas and may guide the surgical strategy.