Seek and destroy. Theranostics of hyperinsulinemic hypoglycemia using exendin-based tracers
Year: 2021
Type: dissertation
Abstract: IntroductionInsulinomas are usually small, benign pancreatic neuroendocrine tumors.Precise anatomical localization is crucial for surgical treatment.The current standard imaging techniques CT, MRI and somatostatin receptor (SSTR) PET have limited sensitivity.The glucagon-like peptide 1 (GLP-1) analog exendin specifically binds to the GLP-1 receptor, which is overexpressed in most insulinomas.We have performed a prospective multicenter imaging study to compare the effectiveness of [ 68 Ga]Ga-NODAGA-exendin-4 PET/CT (GLP-1R PET) with all current standard non-invasive imaging procedures for the localization of insulinomas.Methods 42 adults aged 24-62 with biochemically proven hyperinsulinemic hypoglycemia were included.PET/CT images were obtained one and two hours after injection of 95-105 MBq [ 68 Ga]Ga-NODAGA-exendin-4 (5-7 µg).Current standard imaging, consisting of CT or MRI and SSTR PET, was performed within 8 weeks of GLP-1R PET in all patients.A patient-based analysis was performed with histopathology as a reference standard.Tumor-to-background ratios and contrast-to-noise ratios were determined by quantitative analysis of GLP-1R and SSTR PET images by a blinded observer. ResultsLesions were identified in 33 patients.31 patients underwent surgery and presence of an insulinoma was confirmed histopathologically.Analysis showed that GLP-1R PET localized insulinomas with a higher accuracy and sensitivity (90.6% and 93.5% respectively) than conventional imaging (78.1% and 80.6% respectively) and SSTR PET (59.4% and 61.3% respectively).In 12.5% of patients, a correct diagnosis and decision to perform surgery was only reached after GLP-1R PET.Mean tumorto-background ratios were 12.2 ± 3.4 for GLP-1R PET compared to 4.0 ± 3.0 for SSTR PET (p=0.0017) and mean contrast-to-noise ratios were 24.1 ± 20.8 for GLP-1R PET compared to 5.3 ± 4.4 for SSTR PET (p=0.022).The lower peptide dose used in this study compared to previous studies with [ 68 Ga]Ga-DOTA-exendin-4 (4-7 µg vs. 12-24 µg respectively) resulted in fewer occurrences of nausea (5% vs. 27% of patients). ConclusionThis study demonstrates the superior performance of GLP-1R PET/CT compared to current standard non-invasive imaging modalities for pre-operative localization of benign insulinomas.GLP-1R PET significantly influenced the clinical management of the patients in this population.Because of its high sensitivity and excellent imaging quality, GLP-1R PET/CT could have the potential to be used as the primary diagnostic imaging modality in patients with AHH.
Author: Boss, M.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6996524182