In the operating room: pediatric surgeon Prof. Steven Warmann/Photo: Charité
Charité team establishes more gentle surgery for localized, focal hyperinsulinism
Berlin, October 9, 2025
When children are born with hyperinsulinism, the pancreas produces too much insulin, and the newborn’s blood sugar levels can drop to life-threatening levels. Rapid action is then required. This requires precise diagnostics – which presents some challenges. An interdisciplinary team at the Charité – Universitätsmedizin Berlin has now developed a new, simpler, and therefore faster and gentler diagnostic and surgical method, which is currently only routinely used at the Charité worldwide.
Congenital hyperinsulinism is a rare, genetic metabolic disorder in which too much insulin is produced. Too much insulin means too little sugar in the blood, which leads to dangerous and recurring hypoglycemia. Because the condition is present from birth, it must be diagnosed and treated quickly to prevent permanent nerve damage and later cognitive impairment.
Focal hyperinsulinism treatable with surgery
Treatment depends on the form of the condition. If the entire pancreas is affected, lifelong drug therapy is usually necessary. However, in the so-called focal form, which only affects a localized area, a cure is possible. “If not all insulin-producing cells in the pancreas are affected, we can treat hyperinsulinism very effectively with surgery in most cases,” explains Prof. Peter Kühnen, Director of the Department of Pediatric Endocrinology and Diabetology at the Charité.
However, such an operation presents many challenges: The affected region is usually only a few millimeters in size and must first be precisely identified. “If too much of the pancreas is removed, it can lead to diabetes in the long term,” says Peter Kühnen. At the same time, the removal must be complete, because even small remnants of affected tissue can be enough to prevent healing.
New substance for PET-MRI imaging
To identify the affected areas, a so-called PET-MRI is used as an imaging technique, a combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) in nuclear medicine. This procedure previously involved the introduction of the radioactively labeled substance 18-F-DOPA – a so-called tracer – into the body. The distribution of the tracer, which accumulates where certain metabolic processes are particularly active, allows the affected area to be identified in the images. The team led by Prof. Winfried Brenner, Head of the Department of Nuclear Medicine at the Charité, is responsible for this part of the procedure.
However, this method has its pitfalls: The pancreas is often in a different position during surgery than during the examination. This displacement of the pancreas, coupled with the high uptake of the tracer substance in the adjacent liver, can make visualization of the affected tissue difficult. Furthermore, the production of 18-F-DOPA is complex, and the substance is unavailable or hardly available in developing and emerging countries.
Therefore, the Charité team, in cooperation with Dutch colleagues from Nijmegen, has established an easier-to-produce alternative tracer for diagnostics, the substance 68-Ga-exendin. In two studies published in the journals EJNMMI Research* and Journal of Nuclear Medicine**, the Charité team was able to demonstrate that this tracer is comparable in quality and reliability to the current standard, 18-F-DOPA.
New method brings benefits for patients
Unlike 18-F-DOPA, the new tracer can also be used during surgery. This allows the affected tissue to be identified and removed very quickly intraoperatively using a probe. This radio-guided surgery approach significantly simplifies and accelerates the operation. “We expect that the new method will also reduce complications,” explains Prof. Steven Warmann. He heads the Department of Pediatric Surgery at the Charité, which is part of the interdisciplinary surgical team. Physicians from the fields of pediatric endocrinology and nuclear medicine are also involved in the procedures.
“So far, the new method is only routinely used at the Charité worldwide,” says Peter Kühnen. “However, we hope that this procedure will be adopted by other centers. The data indicate that this approach can significantly improve diagnostics and treatment.”
* Kühnen P et al. [68Ga] labeled Exendin for radioguided surgery of intrapancreatic insulin producing lesions in patients with congenital hyperinsulinism. EJNMMI Res. 2025 Aug 12. doi: 10.1186/s13550-025-01294-8
**Boss M et al. 68Ga-NODAGA-Exendin-4 PET/CT Improves the Detection of Focal Congenital Hyperinsulinism. J Nucl Med. 2021 Jul 2. doi: 10.2967/jnumed.121.262327
About the Studies
The establishment of the substance 68-Ga-exendin as a new diagnostic option dates back to the EU project Beta-Cure, in which Charité physicians worked closely with the team led by Prof. Martin Gotthardt (Radboud University Nijmegen), which developed the substance exendin prepared for radiolabeling. This project demonstrated that the new tracer substance 68-Ga-exendin exhibits at least a very similar specificity and sensitivity to the previous gold standard, 18-F-DOPA. In the pilot study at Charité, this substance was used to localize the affected areas directly during surgery. It was shown that the affected areas were easier to localize with 68-Ga-exendin, thereby reducing the duration of the operation and complication rates. Key contributors included, among others: Peter Kühnen (pediatric endocrinology), Prof. Karin Rothe, Steven Warmann (both pediatric surgery) and Winfried Brenner (nuclear medicine) as well as Oliver Blankenstein, senior physician in pediatric endocrinology at the Charité, with their teams.