Browsing by Subject "congenital hyperinsulinism"

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  • Boss, Marti; Rottenburger, Christof; Brenner, Winfried; Blankenstein, Oliver; Prasad, Vikas; Prasad, Sonal; de Coppi, Paolo; Kuhnen, Peter; Buitinga, Mijke; Nuutila, Pirjo; Otonkoski, Timo; Hussain, Khalid; Brom, Maarten; Eek, Annemarie; Bomanji, Jamshed; Shah, Pratik; Gotthardt, Martin (2022)
    Surgery with curative intent can be offered to congenital hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled exendin-4 specifically binds the glucagonlike peptide 1 receptor on pancreatic beta-cells. In this study, we compared the performance of F-18-DOPA PET/CT, the current standard imaging method for CHI, and PET/CT with the new tracer Ga-68-NODAGA-exendin-4 in the preoperative detection of focal CHI. Methods: Nineteen CHI patients underwent both F-18-DOPA PET/CT and Ga-68-NODAGA-exendin-4 PET/CT before surgery. The images were evaluated in 3 settings: a standard clinical reading, a masked expert reading, and a joint reading. The target (lesion)-to-nontarget (normal pancreas) ratio was determined using SUVmax. Image quality was rated by pediatric surgeons in a questionnaire. Results: Fourteen of 19 patients having focal lesions underwent surgery. On the basis of clinical readings, the sensitivity of Ga-68-NODAGA-exendin-4 PET/CT (100%; 95% CI, 77%-100%) was higher than that of F-18-DOPA PET/CT (71%; 95% CI, 42%-92%). Interobserver agreement between readings was higher for Ga-68-NODAGA-exendin-4 than for F-18-DOPA PET/CT (Fleiss kappa = 0.91 vs. 0.56). Ga-68-NODAGA-exendin-4 PET/CT provided significantly (P = 0.021) higher target-to-nontarget ratios (2.02 +/- 0.65) than did F-18-DOPA PET/CT (1.40 +/- 0.40). On a 5-point scale, pediatric surgeons rated Ga-68-NODAGA-exendin-4 PET/CT as superior to F-18-DOPA PET/CT. Conclusion: For the detection of focal CHI, Ga-68-NODAGA-exendin-4 PET/CT has higher clinical sensitivity and better interobserver correlation than F-18-DOPA PET/CT. Better contrast and image quality make Ga-68-NODAGA-exendin-4 PET/CT superior to F-18-DOPA PET/CT in surgeons' intraoperative quest for lesion localization.
  • Lithovius, Väinö; Otonkoski, Timo (2022)
    Congenital hyperinsulinism (CHI) is a severe inherited neonatal disorder characterized by inappropriate insulin secretion caused by genetic defects of the pancreatic beta cells. Several open questions remain in CHI research, such as the optimal treatment for the most common type of CHI, caused by mutations in the genes encoding ATP-sensitive potassium channels, and the molecular mechanisms of newly identified CHI genes. Answering these questions requires robust preclinical models, particularly since primary patient material is extremely scarce and accurate animal models are not available. In this short review, we explain why pluripotent stem cell derived islets present an attractive solution to these issues and outline the current progress in stem-cell based modeling of CHI. Stem cell derived islets enable the study of molecular mechanisms of CHI and the discovery of novel antihypoglycemic drugs, while also providing a valuable model to study the biology of variable functional states of beta cells.