Glucagon-like peptide-1 receptor SPECT/CT for the preoperative localization of benign insulinomas

Objectives The surgical removal of insulinomas is hampered by the difficulty to localize these tumors using conventional radiological procedures (endosonography, MRI and CT). Angiography and intraarterial calcium stimulation and venous sampling (ASVS) has shown to improve sensitivity but is an invasive procedure with corresponding risks. In vitro data suggest that human insulinoma cells exhibit a high density of glucagon-like peptide-1 (GLP-1) receptors that can be used as specific targets for in vivo receptor imaging. The aim of this study was to evaluate the diagnostic value of GLP-1 receptor imaging with a radiolabeled GLP-1 receptor agonist, 111In-DTPA-exendin-4, in 29 patients with neuroglycopenic symptoms.

Methods Twenty nine patients (18 females, 11 males) with neuroglycopenic symptoms due to endogenous hyperinsulinemic hypoglycemia were consecutively enrolled in this prospective multicenter study. CT or MRI was performed in 27 patients using a standard protocol. 111In-DTPA-exendin-4 was administered intravenously at a dose of 90 - 130 MBq (about 10 μg peptide) over 2 min. Whole-body planar images and SPECT/CT of the abdomen were performed at 4, 24 and in some patients between 72 and 96 hours. Diagnosis was confirmed by histology after surgical removal.

Results In pair-wise comparison, GLP-1 receptor imaging showed a significantly higher performance (sensitivity 100%, PPV 85%) than CT and MRI together (sensitivity 36%, 95% confidence interval 27 - 47%, PPV 100%, P < 0.001). 111In-DTPA-exendin-4 SPECT/CT detected 23 insulinomas and four additional positive lesions (2 islets hyperplasia, 2 uncharacterized lesions). True negative tests were detected in 2 patients. There was no false negative result.

Conclusions GLP-1 receptor imaging defines a novel non-invasive method that may replace the invasive approach (ASVS) to localize occult benign insulinomas